TÍTULO / TITLE: - Alzheimer’s-related endosome dysfunction in Down syndrome is A{beta}-independent but requires APP and is reversed by BACE-1 inhibition.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- Proc Natl Acad Sci U S A. 2009 Dec 28.
AUTORES / AUTHORS:
- Jiang Y; Mullaney KA; Peterhoff CM; Che S; Schmidt SD; Boyer-Boiteau A; Ginsberg SD; Cataldo AM; Mathews PM; Nixon RA
INSTITUCIÓN / INSTITUTION:
- Center for Dementia Research, Nathan Kline Institute, Orangeburg, NY 10962 Departments of Psychiatry Physiology and Neuroscience Cell Biology, Langone School of Medicine, New York University, New York, NY 10016 Laboratory for Molecular Neur
RESUMEN / SUMMARY:
- An additional copy of the beta-amyloid precursor protein (APP) gene causes early-onset Alzheimer’s disease (AD) in trisomy 21 (DS). Endosome dysfunction develops very early in DS and AD and has been implicated in the mechanism of neurodegeneration. Here, we show that morphological and functional endocytic abnormalities in fibroblasts from individuals with DS are reversed by lowering the expression of APP or beta-APP-cleaving enzyme 1 (BACE-1) using short hairpin RNA constructs. By contrast, endosomal pathology can be induced in normal disomic (2N) fibroblasts by overexpressing APP or the C-terminal APP fragment generated by BACE-1 (betaCTF), all of which elevate the levels of betaCTFs. Expression of a mutant form of APP that cannot undergo beta-cleavage had no effect on endosomes. Pharmacological inhibition of APP gamma-secretase, which markedly reduced Abeta production but raised betaCTF levels, also induced AD-like endosome dysfunction in 2N fibroblasts and worsened this pathology in DS fibroblasts. These findings strongly implicate APP and the betaCTF of APP, and exclude Abeta and the alphaCTF, as the cause of endocytic pathway dysfunction in DS and AD, underscoring the potential multifaceted value of BACE-1 inhibition in AD therapeutics.
TÍTULO / TITLE:
- Alzheimer A{beta} Peptide Induces Chromosome Mis-Segregation and Aneuploidy, Including Trisomy 21; Requirement for Tau and APP.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Mol Biol Cell. 2009 Dec 23.
AUTORES / AUTHORS:
- Granic A; Padmanabhan J; Norden M; Potter H
INSTITUCIÓN / INSTITUTION:
- Eric Pfeiffer Suncoast Alzheimer’s Center, Byrd Alzheimer’s Institute, Florida Alzheimer’s Disease Research Center, Department of Molecular Medicine, College of Medicine, School of Aging Studies, College of Behavioral and Community Sciences
RESUMEN / SUMMARY:
- Monitoring Editor: Yixian Zheng Both sporadic and familial Alzheimer’s disease patients exhibit increased chromosome aneuploidy, particularly trisomy 21, in neurons and other cells. Significantly, trisomy 21/Down syndrome patients develop early onset AD pathology. We investigated the mechanism underlying mosaic chromosome aneuploidy in AD and report that FAD mutations in the Alzheimer Amyloid Precursor Protein gene, APP, induce chromosome mis-segregation and aneuploidy in transgenic mice and in transfected cells. Furthermore, adding synthetic Abeta peptide, the pathogenic product of APP, to cultured cells causes rapid and robust chromosome mis-segregation leading to aneuploid, including trisomy 21, daughters, which is prevented by LiCl addition or Ca++ chelation and is replicated in tau KO cells, implicating GSK-3beta, calpain, and Tau-dependent microtubule transport in the aneugenic activity of Abeta. Furthermore, APP KO cells are resistant to the aneugenic activity of Abeta, as they have been shown previously to be resistant to Abeta-induced tau phosphorylation and cell toxicity. These results indicate that Abeta-induced microtubule dysfunction leads to aneuploid neurons and may thereby contribute to the pathogenesis of Alzheimer’s disease.
TÍTULO / TITLE:
- Communication breaks-Down: from neurodevelopment defects to cognitive disabilities in Down syndrome.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- Prog Neurobiol. 2010 Jan 21.
AUTORES / AUTHORS:
- Contestabile A; Benfenati F; Gasparini L
INSTITUCIÓN / INSTITUTION:
- Department of Neuroscience and Brain Technologies, The Italian Institute of Technology, Via Morego 30, 16163 Genova, Italy.
RESUMEN / SUMMARY:
- Down syndrome (DS) is the leading cause of genetically-defined intellectual disability and congenital birth defects. Despite being one of the first genetic diseases identified, only recently, thanks to the phenotypic analysis of DS mouse genetic models, we have begun to understand how trisomy may impact cognitive function. Cognitive disabilities in DS appear to result mainly from two pathological processes: neurogenesis impairment and Alzheimer-like degeneration. In DS brain, suboptimal network architecture and altered synaptic communication arising from neurodevelopmental impairment seem to be key determinants of cognitive defects. Hypocellularity and hypoplasia start at early developmental stages and likely depend upon impaired proliferation of neuronal precursors, resulting in reduction of numbers of neurons and synaptic contacts. The impairment of neuronal precursor proliferation appears to extend to adult neurogenesis and may affect learning and memory. Neurodegenerative mechanisms also contribute to DS cognitive impairment. Early onset Alzheimer disease occurs with an extremely high incidence in DS patients and is causally-related to overexpression of beta-amyloid precursor protein (betaAPP), which is one of the triplicated genes in DS. In this review, we survey the available findings on neurodevelopmental and neurodegenerative changes occurring in DS throughout life. Moreover, we will discuss the potential mechanisms by which defects in neurogenesis and neurodegenerative processes lead to altered formation of neural circuits and impair cognitive function, in connection with findings on pharmacological treatments of potential benefit for DS.
TÍTULO / TITLE:
- Early Age at Menopause is Associated with Increased risk of Dementia and Mortality in Women with Down Syndrome.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- J Alzheimers Dis. 2010;19(2):545-50.
AUTORES / AUTHORS:
- Coppus AM; Evenhuis HM; Verberne GJ; Visser FE; Eikelenboom P; van Gool WA; Janssens AC; van Duijn CM
INSTITUCIÓN / INSTITUTION:
- Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, The Netherlands Dichterbij, Centre for the Intellectually Disabled, Gennep, The Netherlands.
RESUMEN / SUMMARY:
- In a prospective longitudinal cohort study of dementia and mortality in persons with Down syndrome aged 45 years and older, 85 postmenopausal women were followed for a mean follow-up time of 4.3 years (range 0.0 to 7.4 years). The effect of age at menopause on age at diagnosis of dementia and survival was estimated using correlation analysis and Cox Proportional Hazard Model. We found a significant correlation between age at menopause and age at diagnosis of dementia (rho=0.52; p< 0.001), and between age at menopause and age at death (rho=0.49; p=0.01). Early age at menopause is associated with a 1.8 fold increased risk of dementia: Hazard Ratio (HR): 1.82 (95%Confidence Interval (CI): 1.31-2.52) and with risk of death: HR: 2.05 (95%CI: 1.33-3.16). Our study suggests that age at menopause in women with Down syndrome is a determinant of age at onset of dementia and mortality.
TÍTULO / TITLE:
- Transactive response DNA-binding protein 43 burden in familial Alzheimer disease and Down syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Arch Neurol. 2009 Dec;66(12):1483-8.
AUTORES / AUTHORS:
- Lippa CF; Rosso AL; Stutzbach LD; Neumann M; Lee VM; Trojanowski JQ
INSTITUCIÓN / INSTITUTION:
- Drexel University College of Medicine Philadelphia, Philadelphia, Pennsylvania 19102, USA
clippa@drexelmed.edu
RESUMEN / SUMMARY:
- OBJECTIVE: To assess the transactive response DNA-binding protein 43 (TDP-43) burden in familial forms of Alzheimer disease (FAD) and Down syndrome (DS) to determine whether TDP-43 inclusions are also present. DESIGN: Using standard immunohistochemical techniques, we examined brain tissue samples from 42 subjects with FAD and 14 with DS. RESULTS: We found pathological TDP-43 aggregates in 14.0% of participants (6 of 42 and 2 of 14 participants with FAD and DS, respectively). In both FAD and DS, TDP-43 immunoreactivity did not colocalize with neurofibrillary tangles. Occasionally participants with FAD or DS had TDP-43-positive neuropil threads or dots. Overall, the amygdala was most commonly affected, followed by the hippocampus, with no TDP-43 pathology in neocortical regions. A similar distribution of TDP-43 inclusions is seen in sporadic Alzheimer disease, but it differs from that seen in amyotrophic lateral sclerosis and frontotemporal dementia. CONCLUSIONS: Transactive response DNA-binding protein 43 pathology occurs in FAD and DS, similar to that observed in sporadic Alzheimer disease. Thus, pathological TDP-43 may contribute the cognitive impairments in familial and sporadic forms of Alzheimer disease.
TÍTULO / TITLE:
- Atrioventricular septal defect with tetralogy of Fallot in patient with Down’s syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Rev Bras Cir Cardiovasc. 2009 Sep;24(3):422-4.
AUTORES / AUTHORS:
- Jacob MF; De Marchi CH; Croti UA; Braile DM
RESUMEN / SUMMARY:
- Pediatric Cardiovascular Surgery Service of Sao Jose do Rio Preto - Hospital de Base - Faculdade de Medicina de Sao Jose do Rio Preto, Brazil.
TÍTULO / TITLE:
- Marfan syndrome masked by Down syndrome?
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Neth Heart J. 2009 Sep;17(9):345-8.
AUTORES / AUTHORS:
- Vis JC; van Engelen K; Timmermans J; Hamel BC; Mulder BJ
INSTITUCIÓN / INSTITUTION:
- Department of Cardiology, Academic Medical Center, Amsterdam, the Netherlands.
RESUMEN / SUMMARY:
- Down syndrome is the most common chromosomal abnormality. A simultaneous occurrence with Marfan syndrome is extremely rare. We present a case of a 28-year-old female with Down syndrome and a mutation in the fibrillin-1 gene. The patient showed strikingly few manifestations of Marfan syndrome. Although variable expression is known to be present in Marfan syndrome, phenotypic expression of Marfan syndrome in our patient might be masked by the co-occurrence of Down syndrome. (Neth Heart J 2009;17:345-8.).
TÍTULO / TITLE:
- Treating the special needs patient with a developmental disability: cerebral palsy, autism and Down syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Dent Assist. 2009 Nov-Dec;78(6):7-8, 10-1, 34 passim.
AUTORES / AUTHORS:
- Jaccarino J
INSTITUCIÓN / INSTITUTION:
- Department of Allied Dental Education, School of Health Related Professions, University of Medicine and Dentistry of New Jersey, USA.
jaccarja@umdnj.edu
RESUMEN / SUMMARY:
-
TÍTULO / TITLE:
- Diabetic ketoacidosis, thyroiditis and alopecia areata in a child with down syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Indian J Pediatr. 2009 Dec;76(12):1263-4. Epub 2009 Dec 11.
AUTORES / AUTHORS:
- Pirgon O; Atabek ME; Sert A
INSTITUCIÓN / INSTITUTION:
- Department of Pediatric Endocrinology, Konya Research and Training Hospital, Konya, Turkey,
ozpirgon@hotmail.com
RESUMEN / SUMMARY:
- A 10-year-old girl with Down syndrome and alopecia areata was admitted with severe ketoacidosis. She had high blood glucose level: 615 mg/dL and her HbAlc level was 13.3 %. After the control of ketoacidosis and reduction of the plasma glucose level, we found low free T4 level and high TSH levels. Thyroid peroxidase antibodies titer was 1383 IU/mL and both gliadin and endomysial antibodies were negative. This was the first report of a child with Down syndrome showing type 1 diabetes combined with alopecia areata and autoimmune thyroid disease.
EAR/NASAL - OTORRINOLARINGOLOGÍA
TÍTULO / TITLE:
- UK and Ireland experience of cochlear implants in children with Down Syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Int J Pediatr Otorhinolaryngol. 2009 Dec 23.
AUTORES / AUTHORS:
- Hans PS; England R; Prowse S; Young E; Sheehan PZ
INSTITUCIÓN / INSTITUTION:
- ENT and Hearing Clinic for Children with Down Syndrome, Department of Paediatric Otorhinolaryngology, Royal Manchester Children’s Hospital, Oxford Road, Manchester M13 9WL, United Kingdom.
RESUMEN / SUMMARY:
- OBJECTIVES: Down Syndrome (DS) is associated with a high incidence of hearing loss. The majority of hearing loss is conductive, but between 4 and 20% is sensorineural, which in the main is mild or moderate and is managed with conventional behind-the-ear hearing aids. Cochlear implantation is an elective invasive procedure, performed to provide some form of hearing rehabilitation in individuals with severe to profound sensorineural hearing loss, and initially candidacy criteria were strict-excluding patients with additional disabilities. With good results and expanding experience, more candidates with additional disabilities are now being implanted. A survey of UK and Ireland Cochlear Implant Programmes sought to identify the number of individuals with DS who have been implanted with a cochlear implant (CI) and to provide relevant information on outcomes of implantation in these individuals. METHODS: E-mail survey of all programmes within the British Cochlear Implant Group (BCIG). Postal questionnaire to programmes identified to have implanted a child with Down Syndrome, with data collection on pre-operative assessment, surgical and post-operative outcomes. Case series review. RESULTS: Three of 23 BCIG programmes have implanted a child with Down Syndrome. Four children have received implants. No intraoperative or post-operative surgical complications were encountered. All children had middle ear disease, but no problems with implantation were associated with their middle ear condition. All children remain implant users, 12 months to 4 years post-implantation. CONCLUSION: Cochlear implantation is an option for a child with Down Syndrome and associated severe to profound sensorineural hearing loss. Clinicians caring for these children and their families should consider referral for assessment by a Cochlear Implant Programme.
TÍTULO / TITLE:
- Effects of adeno-tonsillectomy on polysomnography patterns in Down syndrome children with obstructive sleep apnea: A comparative study with children without Down syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Int J Pediatr Otorhinolaryngol. 2010 Jan 22.
AUTORES / AUTHORS:
- Shete MM; Stocks RM; Sebelik ME; Schoumacher RA
INSTITUCIÓN / INSTITUTION:
- Otolaryngology & Head and Neck Surgery, University Tennessee Health Science Center, 910 Madison Ave, Suite 429, Memphis, TN 38163, United States.
RESUMEN / SUMMARY:
- OBJECTIVE: To determine if adeno-tonsillectomy (T&A) in children with Down syndrome (DS) improves breathing, measured by apnea hypopnea index (AHI), rapid eye movement AHI (REM-AHI) and the lowest oxygen desaturation (SaO(2)), and sleep disruption, measured by arousal index (ArI) and time spent in stages 1-4 and rapid eye movement (REM) sleep and compare these results with a group of non-DS children with obstructive sleep apnea (OSA). STUDY DESIGN: Retrospective chart review at pediatric sleep center. PATIENTS: Eleven DS and nine non-DS children underwent pre- and post-T&A polysomnography between 1997 and 2005. OUTCOME MEASURES: Pre- and post-T&A polysomnography parameters were compared using paired t-test and independent samples test. RESULTS: Mean age in DS group was 101 months and non-DS group was 80 months (64% males in DS and 88% in non-DS group). The average BMI was 29.8 and 27.6 for DS and non-DS group. The total AHI showed significant improvement after T&A but this was not as marked as the non-DS group. REM-AHI and lowest SaO(2) did not show significant change in the DS children. The non-DS group showed significant improvement in all respiratory parameters. Both groups showed mild improvement in sleep parameters. With the modest overall improvement, 27% of the DS children required no further treatment. However, 73% required CPAP, BiPAP or oxygen for persistent OSA. CONCLUSION: This study supports the fact that T&A in DS children improves some parameters of OSA, however not as markedly as in non-DS children.
ENDOCRINOLOGY/NUTRITION - ENDOCRINOLOGÍA/NUTRICIÓN
TÍTULO / TITLE:
- Diabetic ketoacidosis, thyroiditis and alopecia areata in a child with down syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Indian J Pediatr. 2009 Dec;76(12):1263-4. Epub 2009 Dec 11.
AUTORES / AUTHORS:
- Pirgon O; Atabek ME; Sert A
INSTITUCIÓN / INSTITUTION:
- Department of Pediatric Endocrinology, Konya Research and Training Hospital, Konya, Turkey
ozpirgon@hotmail.com
RESUMEN / SUMMARY:
- A 10-year-old girl with Down syndrome and alopecia areata was admitted with severe ketoacidosis. She had high blood glucose level: 615 mg/dL and her HbAlc level was 13.3 %. After the control of ketoacidosis and reduction of the plasma glucose level, we found low free T4 level and high TSH levels. Thyroid peroxidase antibodies titer was 1383 IU/mL and both gliadin and endomysial antibodies were negative. This was the first report of a child with Down syndrome showing type 1 diabetes combined with alopecia areata and autoimmune thyroid disease.
TÍTULO / TITLE:
- Peculiarities of Graves’ disease in children and adolescents with Down’s syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Eur J Endocrinol. 2009 Dec 2.
AUTORES / AUTHORS:
- De Luca F; Corrias A; Salerno M; Wasniewska M; Gastaldi R; Cassio A; Mussa A; Aversa T; Radetti G; Arrigo T
INSTITUCIÓN / INSTITUTION:
- F De Luca, Department of Pediatrics, University of Messina, Messina, Italy.
RESUMEN / SUMMARY:
- Objective: To compare the presentation and clinical course of Graves’ disease (GD) in two pediatric populations consisting of 28 patients with Down’s syndrome (DS) and 109 controls without DS, respectively. Design and Methods: The evolution over time of GD was determined in both groups according to the clinical changes and the variations in TSH, FT4 and TRAB serum levels during the entire follow-up. Results: Female prevalence (50 vs 81.6%; chi2=12.0, p<0.0005) and average age at GD presentation (9.9 +/- 4.4 vs 11.5 +/- 3.5 yrs, p<0.05) were significantly lower in DS group than in controls. Clinical responsiveness to methimazole therapy was significantly better in DS patients, as demonstrated by both the lower relapse rates after the 1st cycle withdrawal (7.1 vs 31.2%; chi2=7.4, p<0.005) and the higher persistent remission rates after definitive therapy withdrawal (46.4 vs 26.7%; chi2=4.1, p<0.05). Moreover in DS group no patients needed surgery or radioiodine ablation, whereas non-pharmacological treatment was necessary in 11% of controls (chi2=3.8, p<0.05). Antecedents of Hashimoto’s thyroiditis (HT) were documented in 21.4% of DS patients and in 3.7% of controls (chi2=10.4, p<0.005). Association with other autoimmune diseases was detected in 32.1% of DS cases and in 12.8% of controls (chi2=5.94, p<0.025). Conclusions: GD in DS children and adolescents is characterized by several peculiarities: a) earlier presentation; b) no gender predominance; c) less severe clinical course; d) higher frequency of documented HT antecedents; e) more frequent association with other autoimmune diseases.
TÍTULO / TITLE:
- Late effects of early growth hormone treatment in Down syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Acta Paediatr. 2010 Jan 25.
AUTORES / AUTHORS:
- Myrelid A; Bergman S; Elfvik Stromberg M; Jonsson B; Nyberg F; Gustafsson J; Anneren G
INSTITUCIÓN / INSTITUTION:
- Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
RESUMEN / SUMMARY:
- Abstract Objective: Down syndrome (DS) is associated with short stature and psychomotor delay. We have previously shown that growth hormone (GH) treatment during infancy and childhood normalizes growth velocity and improves fine motor skill performance in DS. The aim of this study was to investigate late effects of early GH treatment on growth and psychomotor development in the DS subjects from the previous trial. Design: Twelve of 15 adolescents with DS (3 F) from the GH group and 10 of 15 controls (5 F) participated in this follow-up study. Fifteen other subjects with DS (6 F) were included as controls in anthropometric analyses. Cognitive function was assessed with the Leiter International Performance Scale-Revised (Leiter-R) and selected subtests of the Wechsler Intelligence Scale for Children, Third edition (WISC-III). The Bruininks-Oseretsky Test of Motor Proficiency, Second edition (BOT-2), was used to assess general motor ability. Results: Although early GH treatment had no effect on final height, the treated subjects had a greater head circumference standard deviation score (SDS) than the controls (-1.6 SDS vs. -2.2 SDS). The adolescents previously treated with GH had scores above those of the controls in all subtests of Leiter-R and WISC-III, but no difference in Brief IQ-score was seen between the groups. The age-adjusted motor performance of all subjects was below -2 SD, but the GH-treated subjects performed better than the controls in all but one subtest. Conclusion: The combined finding of a greater head circumference SDS and better psychomotor performance indicates that DS subjects may benefit from early GH treatment.
TÍTULO / TITLE:
- Normal growth hormone secretion in overweight young adults with Down syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Growth Horm IGF Res. 2009 Dec 18.
AUTORES / AUTHORS:
- Myrelid A; Frisk P; Stridsberg M; Anneren G; Gustafsson J
INSTITUCIÓN / INSTITUTION:
- Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
Down syndrome (DS) is associated with short stature and obesity. Adults with DS have several features in common with growth hormone (GH) deficient adu
RESUMEN / SUMMARY:
- Down syndrome (DS) is associated with short stature and obesity. Adults with DS have several features in common with growth hormone (GH) deficient adult subjects. The aim of this study was to investigate GH secretion in young adults with DS and its relation to body composition as well as glucose and lipid metabolism. Ten young adults with DS (aged 24-32years; 5 F) and ten controls matched for age and sex were examined regarding spontaneous nocturnal GH secretion and body composition. Stable isotope tracers were used to study glucose and lipid metabolism in the DS subjects. There was no difference in secretion of GH between the DS subjects and controls. The DS subjects had a higher BMI, fat mass proportion and HOMA (homeostasis model assessment) index compared with the controls. The rates of production of glucose and glycerol (reflecting lipolysis) in the DS subjects were increased (15.5+/-5.07 and 3.5+/-1.68mumol/kg/min, respectively). The DS subjects showed normal GH secretion despite increased BMI and fat mass. The increased HOMA index and high rate of glucose production indicate peripheral and hepatic insulin resistance in adult DS subjects.
TÍTULO / TITLE:
- Prevalence of Down syndrome among children and adolescents in 10 regions of the United States.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Pediatrics. 2009 Dec;124(6):1565-71.
AUTORES / AUTHORS:
- Shin M; Besser LM; Kucik JE; Lu C; Siffel C; Correa A
INSTITUCIÓN / INSTITUTION:
- Division of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
mshin@cdc.gov
RESUMEN / SUMMARY:
- OBJECTIVE: We aimed to estimate the prevalence of Down syndrome (DS) among children and adolescents aged 0 to 19 years in 10 regions of the United States. METHODS: This study was a cross-sectional analysis of live-born infants with DS during 1979-2003 from 10 population-based birth defects registries in the United States. We estimated the prevalence of DS at birth and among children aged 0 to 19 years in each region and in all regions pooled. The prevalence of DS among children and adolescents was calculated overall and according to age group, race/ethnicity, infant gender, and presence of a major heart defect. RESULTS: From 1979 through 2003, the prevalence of DS at birth increased by 31.1%, from 9.0 to 11.8 per 10000 live births in 10 US regions. In 2002, the prevalence among children and adolescents (0-19 years old) was 10.3 per 10000. The prevalence of DS among children in a given age group consistently increased over time but decreased with age within a given birth cohort. The pooled prevalence of DS among children and adolescents was lower among non-Hispanic black individuals and other racial/ethnic groups compared with non-Hispanic white individuals; it was also lower among females than males. CONCLUSIONS: This study provides prevalence estimates of DS among children and adolescents from 10 US regions. These estimates varied according to region, race/ethnicity, and gender, suggesting possible variation in prevalence at birth or in survival rates on the basis of these characteristics.
TÍTULO / TITLE:
- Survival of Texas infants born with trisomies 21, 18, and 13.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Am J Med Genet A. 2010 Jan 15;152A(2):360-366.
AUTORES / AUTHORS:
- Vendola C; Canfield M; Daiger SP; Gambello M; Hashmi SS; King T; Noblin SJ; Waller DK; Hecht JT
INSTITUCIÓN / INSTITUTION:
- Kaiser Permanente, San Jose Medical Center, San Jose, California.
RESUMEN / SUMMARY:
- Trisomies 21, 18, and 13 are the three most common trisomies among infants who survive to 20 weeks gestation or more. Overall information about birth prevalence, natural history, and mortality for all three trisomies is well defined, but information about ethnic-specific rates is limited. Only a few studies have examined mortality rates of trisomies 18 and 13 because so few cases are liveborn and most have very short life spans. This study assessed ethnic-specific population-based survival probabilities among infants for each trisomy. All cases of trisomies 21, 18, and 13 born in Texas between 1999 and 2003 were obtained from the Texas Birth Defects Registry and included 2,260 cases of trisomy 21, 398 cases of trisomy 18, and 213 cases of trisomy 13. Date and cause of death were obtained from the Texas vital statistics records and the National Death Index. Overall, birth prevalence rates (per 10,000 adjusted live births) for the three trisomies were 11.74 (95% CI: 11.25-12.25), 1.34 (95% CI: 1.18-1.52), 0.92 (95% CI: 0.79-1.07), respectively, and are consistent with previously reported rates. There were no differences in survival rates by ethnicity and the median survival for each trisomy was consistent with previous reports. The results of this study provide comprehensive population-based information for survival of infants with trisomies 21, 18, and 13.
GASTROENTEROLOGY - GASTROENTEROLOGÍA
TÍTULO / TITLE:
- Clinical features of Hirschsprung’s disease associated with Down syndrome: a 30-year retrospective nationwide survey in Japan.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- J Pediatr Surg. 2009 Dec;44(12):2347-51.
AUTORES / AUTHORS:
- Ieiri S; Higashi M; Teshiba R; Saeki I; Esumi G; Akiyoshi J; Nakatsuji T; Taguchi T
INSTITUCIÓN / INSTITUTION:
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Kyushu University, Fukuoka 812-8582, Japan.
satoshi@med.kyushu-u.ac.jp
RESUMEN / SUMMARY:
- PURPOSE: To identify the clinical features in diagnosis and treatment of Hirschsprung’s disease (HD) associated with Down syndrome (DS), the authors retrospectively analyzed data for patients with DS from the past 3 nationwide surveys in Japan. This survey was already approved by the Japanese Society of Pediatric Surgeons. METHODS: Patient data were collected in 3 phases-phase I (1978-1982), n = 47; phase II (1988-1992), n = 79; and phase III (1998-2002), n = 90. In total, data on 216 patients (5.6%) of 3852 were collected and analyzed. RESULTS: The incidence of DS in patients with HD was 2.9%, 7.1%, and 8.2% in phases I, II, and III, respectively, with a corresponding male/female ratio of 5:1, 2.4:1, and 5:1. The ratio of the extent of aganglionosis was nearly consistent across all phases. In phases I, II, and III, the incidence of total colonic aganglionosis was 2.1%, 0%, and 2.2%; and that of cardiovascular anomalies, 36.1%, 45.6%, and 55.6%; and that of preoperative enterocolitis, 31.0%, 26.6%, and 24.4%. The 2 most common surgical procedures were the Soave procedure, including transanal endorectal pull-through, and Duhamel procedure including Z-shaped anastomosis. The mortality rate decreased over time, from 26.1% in phase I to 11.4% in phase II and 7.8% in phase III. Almost all mortality cases were associated with cardiovascular anomalies: 54.5%, 62.5%, and 85.7% in phases I, II, and III, respectively. CONCLUSIONS: The incidence of HD with DS has increased over time. The number of male patients and cardiac anomalies has also increased in the last 10 years. Total colonic aganglionosis was rare. A marked decrease in the overall mortality rate was observed.
TÍTULO / TITLE:
- Clinical features of Hirschsprung’s disease associated with Down syndrome: a 30-year retrospective nationwide survey in Japan.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- J Pediatr Surg. 2009 Dec;44(12):2347-51.
AUTORES / AUTHORS:
- Ieiri S; Higashi M; Teshiba R; Saeki I; Esumi G; Akiyoshi J; Nakatsuji T; Taguchi T
INSTITUCIÓN / INSTITUTION:
- Department of Pediatric Surgery, Reproductive and Developmental Medicine, Kyushu University, Fukuoka 812-8582, Japan.
satoshi@med.kyushu-u.ac.jp
RESUMEN / SUMMARY:
- PURPOSE: To identify the clinical features in diagnosis and treatment of Hirschsprung’s disease (HD) associated with Down syndrome (DS), the authors retrospectively analyzed data for patients with DS from the past 3 nationwide surveys in Japan. This survey was already approved by the Japanese Society of Pediatric Surgeons. METHODS: Patient data were collected in 3 phases-phase I (1978-1982), n = 47; phase II (1988-1992), n = 79; and phase III (1998-2002), n = 90. In total, data on 216 patients (5.6%) of 3852 were collected and analyzed. RESULTS: The incidence of DS in patients with HD was 2.9%, 7.1%, and 8.2% in phases I, II, and III, respectively, with a corresponding male/female ratio of 5:1, 2.4:1, and 5:1. The ratio of the extent of aganglionosis was nearly consistent across all phases. In phases I, II, and III, the incidence of total colonic aganglionosis was 2.1%, 0%, and 2.2%; and that of cardiovascular anomalies, 36.1%, 45.6%, and 55.6%; and that of preoperative enterocolitis, 31.0%, 26.6%, and 24.4%. The 2 most common surgical procedures were the Soave procedure, including transanal endorectal pull-through, and Duhamel procedure including Z-shaped anastomosis. The mortality rate decreased over time, from 26.1% in phase I to 11.4% in phase II and 7.8% in phase III. Almost all mortality cases were associated with cardiovascular anomalies: 54.5%, 62.5%, and 85.7% in phases I, II, and III, respectively. CONCLUSIONS: The incidence of HD with DS has increased over time. The number of male patients and cardiac anomalies has also increased in the last 10 years. Total colonic aganglionosis was rare. A marked decrease in the overall mortality rate was observed.
TÍTULO / TITLE:
- Functional Outcome in Children with Hirschsprung`s Disease or Imperforate Anus
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- ZENTRALBLATT FUR CHIRURGIE, 134 (6): 507-513 DEC 2009
AUTORES / AUTHORS:
- Obermayr, F; Fuchs, J
RESUMEN / SUMMARY:
- Various outcomes following operative therapy for Hirschsprung`s disease and anorectal malformations have been reported. Operative techniques for anorectal reconstruction have been modified several times in the past. Repair of anorectal malformations have been performed through a posterior sagittal approach since the 1980s. This allows an anatomically correct reconstruction of the anorectal canal. Abdominoperineal or sacroabdominoperineal pull-through procedures, as the classical operative techniques, have been abandoned by most surgeons. Rectosigmoidectomy with colo-anal anastomosis, as described by Swenson and Bill in 1948, as well as the retro-rectal pull-through (Duhamel) and the endorectal pull-through (Soave) are still frequently used in surgery for Hirschsprung`s disease. The development of the transanal endorectal pull-through with (Georgeson) or without (de la Torre) laparoscopic assistance has eliminated the necessity of laparotomy in selected cases. Despite sign! ificant progress in the understanding of the pathophysiology of and therapy for Hirschsprung`s disease and anorectal malformations, the functional results remain unsatisfactory. Functional problems occur already in early childhood and decrease the quality of life significantly. Although complications resolve with time and the quality of life normalises in adolescence and adulthood, this might be mainly due to an adaptation strategy by the patients. For the future, a standardised and prospective study design is necessary to compare different procedures and to provide a basis for the further development of therapeutic strategies.
TÍTULO / TITLE:
- Down syndrome due to unbalanced homologous acrocentric rearrangements and its recurrence in subsequent pregnancies: prenatal diagnosis by amniocentesis.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Taiwan J Obstet Gynecol. 2009 Dec;48(4):403-7.
AUTORES / AUTHORS:
- Chen CP; Chern SR; Tsai FJ; Wu PC; Chiang SS; Lee CC; Wang W
INSTITUCIÓN / INSTITUTION:
- Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei,Taiwan.
cpc_mmh@yahoo.com
RESUMEN / SUMMARY:
- OBJECTIVE: To present our experience of amniocentesis for the prenatal diagnosis of Down syndrome due to unbalanced homologous acrocentric rearrangements and its recurrence in subsequent pregnancies. CASE REPORT: From January 1987 to September 2009, six cases with rea(21q21q) Down syndrome were diagnosed among 31,194 patients who underwent amniocentesis at Mackay Memorial Hospital, Taipei, Taiwan. Cytogenetic analysis of parental blood lymphocytes was performed in each case, and polymorphic DNA markers were used to investigate the nature of the aberrant chromosome. Three of the six cases were associated with recurrence in subsequent pregnancies. The rea(21q21q) Down syndrome was associated with advanced maternal age in three cases, a previous child with rea(21q21q) Down syndrome in three cases, an abnormal maternal serum screening result in one case, and an abnormal ultrasound finding in one case. All six cases arose de novo. Among the six cases with molecular analysis results, all had isochromosome 21, five of which were determined to be of maternal origin. CONCLUSION: We found a frequency of 0.019% for rea(21q21q) Down syndrome in patients undergoing amniocentesis. Down syndrome caused by the homologous rearrangement rea(21q21q) can be associated with recurrence. Prenatal diagnosis of rea(21q21q) Down syndrome should include extensive cytogenetic and molecular analyses of the parents and probands.
TÍTULO / TITLE:
- Identification of a 21q22 duplication in a Silver-Russell syndrome patient further narrows down the Down syndrome critical region.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
-
AUTORES / AUTHORS:
- Eggermann T; Schonherr N; Spengler S; Jager S; Denecke B; Binder G; Baudis M
INSTITUCIÓN / INSTITUTION:
- Institute of Human Genetics, RWTH Aachen, Aachen, Germany.
RESUMEN / SUMMARY:
- Several duplications of chromosome 21q helped to narrow down the Down syndrome (DS) critical region (DSCR) to chromosomal band 21q22 with an approximate length of 5.4 Mb. Recently, it has been suggested that the facial gestalt of DS has been linked to the distal part of the DSCR whereas the proximal region harboring DSCR1/RCAN and DSCAM should be associated with the cardiac abnormalities. Here, we report on a patient with Silver-Russell syndrome (SRS) and a paternally inherited 0.46 Mb duplication in 21q22 affecting the KCNE1 and DSCR1/RCAN genes. The identification of an involvement of KCNE1 was interesting because it encodes the beta-subunit of the KvLQT1 channel as the slow component of the cardiac delayed rectifier K(+) current. Since duplication of the KCNQ1 gene encoding the alpha-subunit of the same channel was reported recently in another SRS patient, we screened both genes for mutations in a cohort of SRS patients without detecting pathologic variants. We presume that the duplication of the two functionally linked genes in different patients with the same disorder is a coincidental finding. However, the lack of DS typical clinical features in our case allows us to further narrow down the DSCR in 21q22. We conclude that DSCR1/RCAN is not sufficient for generating phenotypic features associated with DS but our observation does not contradict a possible role for DSCR1/RCAN in mediating DYRK1A-based effects.
TÍTULO / TITLE:
- Hay una palabreja que se va difundiendo cada vez más profusamente en la jerga de los psicólogos, siempre prestos a fagocitar y españolizar sin remilgos cualquier término inglés novedoso cuyo concepto
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- REPRODUCTION, 139 (1): 1-9 JAN 2010
AUTORES / AUTHORS:
- Hulten, MA; Patel, S; Jonasson, J; Iwarsson, E
RESUMEN / SUMMARY:
- We have recently documented that trisomy 21 mosaicism is common in human foetal ovaries. On the basis of this observation we propose that the maternal age effect in Down syndrome (DS) is caused by the differential behaviour of trisomy 21 in relation to disomy 21 oocytes during development from foetal life until ovulation in adulthood. in particular, we suggest that trisomy 21 oocytes, lagging behind those that are disomic, may escape the timed pruning of the seven million in foetal life to the 300-400 finally selected for ovulation. The net effect of this preferential elimination will be an accumulation of trisomy 21 oocytes in the ovarian reserve of older women. We here highlight the implications of this Oocyte Mosaicism Selection (OMS) model with respect to the prevalent view that the maternal age effect is complex, dependent on many different biological and environmental factors. We examine conclusions drawn from recent large-scale studies in families, tracing DNA mark! ers along the length of chromosome 21q between parents and DS children, in comparison to the OMS model. We conclude that these family linkage data are equally compatible with the maternal age effect originating from the accumulation of trisomy 21 oocytes with advancing maternal age. One relatively straightforward way to get to grips with what is actually going on in this regard would be to compare incidence of trisomy 21 oocytes (and their pairing configurations) in foetal ovaries with that in oocytes at the meiosis I stage from adult women. Reproduction (2010) 139 1-9
TÍTULO / TITLE:
- Telomere length is associated with types of chromosome 21 nondisjunction: a new insight into the maternal age effect on Down syndrome birth.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Hum Genet. 2010 Jan 10.
AUTORES / AUTHORS:
- Ghosh S; Feingold E; Chakraborty S; Dey SK
INSTITUCIÓN / INSTITUTION:
- Human Genetics Research Unit, School of Biotechnology and Biological Sciences, West Bengal University of Technology, Salt Lake, BF-142, Sector-I, Kolkata, West Bengal, 700064, India.
RESUMEN / SUMMARY:
- Advanced maternal age is a well-documented risk factor of chromosome 21 nondisjunction in humans, but understanding of this association at the genetic level is still limited. In particular, the state of maternal genetic age is unclear. In the present study, we estimated maternal genetic age by measuring telomere length of peripheral blood lymphocytes among age-matched mothers of children with Down syndrome (cases: N = 75) and mothers of euploid children (controls: N = 75) in an age range of 18-42 years. All blood samples were taken within 1 week of the birth of the child in both cases and controls. The telomere length estimation was performed by restriction digestion-Southern blot hybridization method. We stratified the cases on the basis of centromeric STR genotyping into maternal meiosis I (N = 48) and maternal meiosis II (N = 27) nondisjunction groups and used linear regression to compare telomere length as a function of age in the euploid, meiosis I and meiosis II groups. Our results show that all three groups have similar telomere length on average for younger mothers. As age increases, all groups show telomere loss, but that loss is largest in the meiosis II mother group and smallest in the euploid mother group with the meiosis I mother group in the middle. The regression lines for all three were statistically significantly different from each other (p < 0.001). Our results do not support the theory that younger women who have babies with Down syndrome do so because are ‘genetically older’ than their chronological age, but we provide the first evidence that older mothers who have babies with Down syndrome are “genetically older” than controls, who have euploid babies at the same age. We also show for the first time that telomere length attrition may be associated in some way with meiosis I and meiosis II nondisjunction of chromosome 21 and subsequent Down syndrome births at advanced maternal age.
TÍTULO / TITLE:
- Familial small supernumerary marker chromosome (sSMC) (14)(:P11-q11:)In a child with translocation down syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Indian J Pediatr. 2009 Dec;76(12):1265-7. Epub 2009 Dec 11.
AUTORES / AUTHORS:
- Vundinti BR; Korgaonkar S; Ghosh K
INSTITUCIÓN / INSTITUTION:
- Department of Cytogenetics, National Institute of Immunohematology (ICMR) K.E.M. Hospital Campus, Parel, Mumbai, India
vbaburao@hotmail.com
RESUMEN / SUMMARY:
- We report a case of familial small supernumerary marker chromosome (sSMC)in a child with translocation Down syndrome (DS)and mother. The GTG-banded chromosomal analysis of DS child revealed 47,XY,+21,+mar and mother karyotype was 47,XX,+mar. The GTG-banded sSMC had a similar morphology of small acrocentric chromosomes. Fluorescence in situ hybridization (FISH)evaluation of sSMC using centromere probes(13/21,14/22,22)confirmed sSMC as derivative chromosome 14. The sSMC was not specifically stained with whole chromosome paint and arm-specific probes for chromosome 14;thus it has been described as der(14)(:p11-q11:).The phenotypic changes were not evident, may be due to trisomy condition in the child or the sSMC contain repetitive sequences.
TÍTULO / TITLE:
- Investigating the impact of the Down syndrome related common MTHFR 677C>T polymorphism in the Danish population.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Dis Markers. 2009;27(6):279-85.
AUTORES / AUTHORS:
- Kokotas H; Grigoriadou M; Mikkelsen M; Giannoulia-Karantana A; Petersen MB
INSTITUCIÓN / INSTITUTION:
- Department of Genetics, Institute of Child Health, ‘Aghia Sophia’ Children’s Hospital, Athens, Greece.
RESUMEN / SUMMARY:
- Chromosomal aneuploidy consists the leading cause of fetal death in our species. Around 50% of spontaneous abortions until 15 weeks of gestational age are chromosomally aneuploid, with trisomies accounting for 50% of the abnormal abortions. Trisomy 21 is the most common chromosome abnormality in liveborns and is usually the result of nondisjunction of chromosome 21 in meiosis in either oogenesis or spermatogenesis. To investigate the relationship between folate metabolism and Down syndrome (DS) in a Danish population, we analyzed the common 677C>T genetic polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene. Our cohort consisted of 181 mothers of children with DS versus 1,084 healthy controls. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to examine the MTHFR 677C>T polymorphism. No significant association between the polymorphism and the risk for DS was found. We conclude that the common MTHFR 677C>T polymorphism is not likely to be a maternal risk factor for DS in our cohort and that the difference to previous studies can probably be explained by small sample size or geographic variation in gene polymorphisms involving gene-nutritional or gene-gene or gene-nutritional-environmental factors.
GROWTH/DEVELOPMENT - CRECIMIENTO/DESARROLLO
TÍTULO / TITLE:
- Late effects of early growth hormone treatment in Down syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Acta Paediatr. 2010 Jan 25.
AUTORES / AUTHORS:
- Myrelid A; Bergman S; Elfvik Stromberg M; Jonsson B; Nyberg F; Gustafsson J; Anneren G
INSTITUCIÓN / INSTITUTION:
- Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
RESUMEN / SUMMARY:
- Abstract Objective: Down syndrome (DS) is associated with short stature and psychomotor delay. We have previously shown that growth hormone (GH) treatment during infancy and childhood normalizes growth velocity and improves fine motor skill performance in DS. The aim of this study was to investigate late effects of early GH treatment on growth and psychomotor development in the DS subjects from the previous trial. Design: Twelve of 15 adolescents with DS (3 F) from the GH group and 10 of 15 controls (5 F) participated in this follow-up study. Fifteen other subjects with DS (6 F) were included as controls in anthropometric analyses. Cognitive function was assessed with the Leiter International Performance Scale-Revised (Leiter-R) and selected subtests of the Wechsler Intelligence Scale for Children, Third edition (WISC-III). The Bruininks-Oseretsky Test of Motor Proficiency, Second edition (BOT-2), was used to assess general motor ability. Results: Although early GH treatment had no effect on final height, the treated subjects had a greater head circumference standard deviation score (SDS) than the controls (-1.6 SDS vs. -2.2 SDS). The adolescents previously treated with GH had scores above those of the controls in all subtests of Leiter-R and WISC-III, but no difference in Brief IQ-score was seen between the groups. The age-adjusted motor performance of all subjects was below -2 SD, but the GH-treated subjects performed better than the controls in all but one subtest. Conclusion: The combined finding of a greater head circumference SDS and better psychomotor performance indicates that DS subjects may benefit from early GH treatment.
TÍTULO / TITLE:
- Exploratory study: barriers for initiation and/or discontinuation of breastfeeding in mothers of children with Down syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- P R Health Sci J. 2009 Dec;28(4):340-4.
AUTORES / AUTHORS:
- Colon E; Davila-Torres RR; Parrilla-Rodriguez AM; Toledo A; Gorrin-Peralta JJ; Reyes-Ortiz VE
INSTITUCIÓN / INSTITUTION:
- Maternal & Child Health Program, School of Public Health, University of Puerto Rico.
RESUMEN / SUMMARY:
- BACKGROUND: The aim of the study is to identify the barriers associated with breastfeeding in mothers of Puerto Rican children with Down. METHOD: A non-probabilistic sample (n = 26) of mothers was used in the study. The sample was obtained in an institution in Puerto Rico specializing in care of infants with Down Syndrome [IDS]. A self-administered questionnaire was used consisting of six sections. Descriptive statistics were used for data analysis. RESULTS: The majority of interviewed mothers (80.8%) had 70.0% or higher correct answers regarding the benefits of breastfeeding. 84.6% of the mothers who decided not to breastfeed or who discontinued breastfeeding reported as the main reason that the baby presented sucking problems and 50.0% of the participants were not allowed to have their baby with them during their stay in the hospital. 84.3% of the participants indicated having breastfed their IDS and 61.5% stated that they would not breastfeed in public places. CONCLUSION: Active support, instruction, and collaboration among members of the health care team are essential for breastfeeding success.
TÍTULO / TITLE:
- Early Age at Menopause is Associated with Increased risk of Dementia and Mortality in Women with Down Syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- J Alzheimers Dis. 2010;19(2):545-50.
AUTORES / AUTHORS:
- Coppus AM; Evenhuis HM; Verberne GJ; Visser FE; Eikelenboom P; van Gool WA; Janssens AC; van Duijn CM
INSTITUCIÓN / INSTITUTION:
- Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, The Netherlands Dichterbij, Centre for the Intellectually Disabled, Gennep, The Netherlands.
RESUMEN / SUMMARY:
- In a prospective longitudinal cohort study of dementia and mortality in persons with Down syndrome aged 45 years and older, 85 postmenopausal women were followed for a mean follow-up time of 4.3 years (range 0.0 to 7.4 years). The effect of age at menopause on age at diagnosis of dementia and survival was estimated using correlation analysis and Cox Proportional Hazard Model. We found a significant correlation between age at menopause and age at diagnosis of dementia (rho=0.52; p< 0.001), and between age at menopause and age at death (rho=0.49; p=0.01). Early age at menopause is associated with a 1.8 fold increased risk of dementia: Hazard Ratio (HR): 1.82 (95%Confidence Interval (CI): 1.31-2.52) and with risk of death: HR: 2.05 (95%CI: 1.33-3.16). Our study suggests that age at menopause in women with Down syndrome is a determinant of age at onset of dementia and mortality.
TÍTULO / TITLE:
- Precocious puberty in a girl with Down syndrome due to primary hypothyroidism.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Turk J Pediatr. 2009 Jul-Aug;51(4):381-3.
AUTORES / AUTHORS:
- Ozgen T; Guven A; Aydin M
INSTITUCIÓN / INSTITUTION:
- Department of Pediatric Endocrinology, Ondokuz Mayis University Faculty of Medicine, Samsun, Turkey.
RESUMEN / SUMMARY:
- Van Wyk-Grumbach syndrome is a rare cause of precocious puberty due to hypothyroidism. We report a case of Van Wyk-Grumbach syndrome in a 4.3-year-old female patient with Down syndrome. She was investigated for hematuria for three months before she was referred to our clinic. Physical examination revealed typical morphologic features of Down syndrome and hypothyroidism. Pubertal development stages were: breast at stage III and pubic hair at stage I. In luteinizing hormone releasing hormone (LHRH) stimulation test, peak LH level remained less than 0.1 mIU/ml. Serum estradiol level was 117.7 pg/ml, which was higher than normal for her age (normal range: 2-15 pg/ml). The pelvic ultrasonographic evaluation revealed bilateral multicystic enlarged ovaries. Serum thyroid stimulating hormone (TSH) concentration was higher than 500 microIU/ml and free thyroxin (FT4) and free triiodothyronine (FT3) levels were as low as 0.4 ng/dl (0.7-1.48) and 1.0 pg/ml (1.71-3.71), respectively. L-thyroxin treatment at a dose of 100 microg/m2/day was started. Regression in breast development was obtained after one month and her bleeding did not repeat again. In conclusion, urinary and vaginal bleeding in young children must be clearly differentiated, and hypothyroidism must be investigated in children who have precocious puberty.
HEMATOLOGY/ONCOLOGY - HEMATOLOGÍA/ONCOLOGÍA
TÍTULO / TITLE:
- Trisomy of Erg is required for myeloproliferation in a mouse model of Down syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Blood. 2009 Dec 9.
AUTORES / AUTHORS:
- Ng AP; Hyland CD; Metcalf D; Carmichael CL; Loughran SJ; Di Rago L; Kile BT; Alexander WS
INSTITUCIÓN / INSTITUTION:
- Cancer and Haematology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia;
RESUMEN / SUMMARY:
- Down syndrome is characterized by multiple phenotypic manifestations associated with trisomy of chromosome 21. The transient myeloproliferative disorder and acute megakaryocytic leukemia associated with Down syndrome are uniquely associated with mutations in the transcription factor GATA-1; however the identity of trisomic genes on chromosome 21 that predispose to these hematological disorders remain unknown. Utilising a loss of function allele, we show that specific reduction to functional disomy of the Erg gene corrects the pathological and hematological features of myeloproliferation in the Ts(17(16))65Dn mouse model of Down syndrome, including megakaryocytosis and progenitor cell expansion. Our data provide genetic evidence establishing the need for Erg trisomy for myeloproliferation in Ts(17(16))65Dn mice and imply that increased Erg gene dosage may be a key consequence of trisomy-21 that can predispose to malignant hematological disorders in Down syndrome.
TÍTULO / TITLE:
- A comparison of acute lymphoblastic leukemia in Down syndrome and non-Down syndrome children: the role of trisomy 21.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- J Pediatr Oncol Nurs. 2009 Nov-Dec;26(6):362-8.
AUTORES / AUTHORS:
- Tigay JH
INSTITUCIÓN / INSTITUTION:
- University of Flint Michigan, 6550 Heritage, West Bloomfield, MI 48322, USA.
judykay1229@aol.com
RESUMEN / SUMMARY:
- Down syndrome (DS), which occurs once in every 800 births, is associated with a trisomy on locus 21. Among the many aberrations caused by DS, including shortened stature and distorted facies, are several blood dyscrasias, including childhood leukemias-namely, acute myeloid leukemia (AML) and acute lymphoblastic, or lymphocytic, leukemia (ALL). One focus of the diagnosis of ALL is to distinguish it from AML.The benefits of immunophenotyping extend to treatment as well. ALL is associated with an inherited trisomy 21 in DS children (ALL-DS) and with acquired trisomies, +21, 8, and 13, in non-DS children (ALL-NDS). The differences in treatment, outcome, and prognosis between ALL-DS and ALL-NDS can be attributed to the interaction of their respective trisomies with several genetic mutations, including one on the GATA1 growth factor transcription gene. Other mutations are the gene fusion at TEL/AML1, and a new mutation found, which labels the Janus Kinase gene or JAK2 as on oncogenic precursor, which when associated with the B-cell precursor gene or BCP is highly leukomogenic. The treatments for the 2 groups have been based on quality of risk, with ALL-DS children having the highest risk along with the poorest prognosis, but alterations in medication regimens have brought treatment outcomes to near equality. It is worthwhile to study the trisomy 21 because in the future it may provide an understanding of all blood dyscrasias.
TÍTULO / TITLE:
- A rare case of GATA1 negative chemoresistant acute megakaryocytic leukemia in an 8-month-old infant with trisomy 21.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Pediatr Blood Cancer. 2010 Jan 27.
AUTORES / AUTHORS:
- Stepensky P; Brooks R; Waldman E; Revel-Vilk S; Izraeli S; Resnick I; Weintraub M
INSTITUCIÓN / INSTITUTION:
- Department of Pediatric Hematology-Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
RESUMEN / SUMMARY:
- Children with Down syndrome (DS) have a unique form of acute megakaryocytic leukemia (AMKL) characterized by the presence of mutations in the GATA1 gene leading to increased chemosensitivity and a favorable outcome. We describe an 8-month-old male with DS who was diagnosed with AMKL without a mutation in the GATA1 gene. The patient was treated according to the DS-AML-regimen but his disease progressed and he succumbed 9 months later. This rare case of DS AMKL without a GATA1 mutation with an unfavorable outcome suggests that GATA1 testing may play a useful role in initial stratification. Pediatr Blood Cancer. © 2010 Wiley-Liss, Inc.
TÍTULO / TITLE:
- Down syndrome B-lymphocyte subpopulations, intrinsic defect or decreased T-lymphocyte help.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Pediatr Res. 2010 Jan 21.
AUTORES / AUTHORS:
- Verstegen RH; Kusters MA; Gemen EF; de Vries E
INSTITUCIÓN / INSTITUTION:
- Department of Pediatrics [R.H.J.V., M.A.A.K., E.V.], Department of Clinical Chemistry and Hematology [E.F.A.G.], Jeroen Bosch Hospital, ‘s-Hertogenbosch, 5200 ME, The Netherlands.
RESUMEN / SUMMARY:
- Down Syndrome (DS) is known for increased incidence of respiratory infections and autoimmune diseases, indicating impaired immunity. Until now, attention has been mainly focused on T-lymphocytes. Therefore, we determined B-lymphocyte subpopulations in 95 DS-children compared to 33 age-matched controls. DS serum immunoglobulin levels were compared to 962 non-DS-children with recurrent infections. The results were combined with clinical data. Transitional and naive B-lymphocytes are profoundly decreased in the DS children. This could be caused by an intrinsic B-lymphocyte defect resulting in (partial) failure of B-lymphocyte generation, decreased antigen-induced proliferation and/or increased apoptosis, or by decreased proliferation due to deficient T-lymphocyte help, or a combination of these. The decreased CD27, CD21 and CD23 cells are reminiscent of Common Variable Immunodeficiency and suggestive of disturbed peripheral B-lymphocyte maturation. Immunoglobulin levels in DS are abnormal - as has been described before - and different from non-DS children with recurrent infections. We conclude that the humoral immune system is abnormal in DS, but could not find a relation between B-lymphocyte subsets, immunoglobulins and clinical features of the DS children in our cohort, nor could we answer the question whether DS lymphocytes are truly intrinsically deficient, or could all findings be explained by deficient T-lymphocyte help.
TÍTULO / TITLE:
- Catastrophic Antiphospholipidic Syndrome in a child with Trisomy 21. An acquired thrombopathy with a discussion of thrombopathies in childhood.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Pediatr Dev Pathol. 2009 Dec 3.
AUTORES / AUTHORS:
- Dehner LP; Gru Md A
INSTITUCIÓN / INSTITUTION:
- 1 Washington University School of Medicine.
RESUMEN / SUMMARY:
- Abstract Antiphopholipidic syndrome (APLS), an acquired thrombophilic disorder involving autoantibodies against phospholipids (PL) and PL-binding proteins, is often accompanied by autoimmune disease but also occurs in the absence of any documented autoimmune disease. It is known to be more common in individuals with trisomy 21. Catastrophic APLS (CAPLS) a rare accelerated form of APLS, leads to acute multi-system organ failure, with microthrombi in multiple organs and a mortality rate of 50% or greater. The youngest case of APLS was reported in a 7 year old child. We report the pathologic findings in a case of CAPLS in a 2-year-old girl with trisomy 21 who presented with an insidious skin rash which was rapidly followed by multi-organ failure and death. All major criteria for the diagnosis of CAPLS were met including the involvement of 3 or more organs systems, precipitous clinical deterioration, positive serology for APL, and non-inflammatory microthrombi in at least one organ which in this case included multiple sites: skin, lungs, intestinal tract with necrotizing enterocolitis and spleen with multiple infarcts all documented at autopsy.
TÍTULO / TITLE:
- Down syndrome acute lymphoblastic leukemia: a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the iBFM Study Group.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Blood. 2009 Nov 24.
AUTORES / AUTHORS:
- Hertzberg L; Vendramini E; Ganmore I; Cazzaniga G; Schmitz M; Chalker J; Shiloh R; Iacobucci I; Shochat C; Zeligson S; Cario G; Stanulla M; Strehl S;
INSTITUCIÓN / INSTITUTION:
- Pediatric Hemato-Oncology and the Cancer Research Center, Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel;
RESUMEN / SUMMARY:
- We report gene expression and other analyses to elucidate the molecular characteristics of acute lymphoblastic leukemia (ALL) in children with Down Syndrome (DS). We find that by gene expression DS-ALL is a highly heterogeneous disease not definable as a unique entity. Nevertheless, 62% (33/53) of the DS-ALL samples analyzed were characterized by high expression of the type I cytokine receptor CRLF2 caused by either IgH@ translocations or by interstitial deletions creating chimeric transcripts P2RY8-CRLF2. In 3 of these 33 patients a novel activating somatic mutation, F232C in CRLF2 was identified. Consistent with our previous research, mutations in R683 of JAK2 were identified in 10 specimens (19% of the patients) and interestingly all 10 had high CRLF2 expression. CRLF2 and mutated Jak2 cooperated in conferring cytokine independent growth to BaF3 pro-B-cells. Intriguingly the gene expression signature of DS-ALL is enriched with DNA damage and BCL6 responsive genes, suggesting the possibility of B-cell lymphocytic genomic instability. Thus DS confers increased risk for genetically highly diverse ALLs with frequent overexpression of CRLF2, associated with activating mutations in the receptor itself or in JAK2. Our data also suggest that the majority of DS children with ALL may benefit from therapy blocking the CRLF2/JAK2 pathways.
TÍTULO / TITLE:
- Blasts in transient leukaemia in neonates with Down syndrome differentiate into basophil/mast-cell and megakaryocyte lineages in vitro in association with down-regulation of truncated form of GATA1.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Br J Haematol. 2010 Jan 11.
AUTORES / AUTHORS:
- Miyauchi J; Ito Y; Tsukamoto K; Takahashi H; Ishikura K; Sugita K; Miyashita T
INSTITUCIÓN / INSTITUTION:
- Department of Pathology and Laboratory Medicine, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Chiba-ken, Japan.
RESUMEN / SUMMARY:
- Summary Mutations of GATA1, leading to aberrant expression of a truncated form of GATA1 (called GATA1s), are present in transient leukaemia (TL) in neonates with Down syndrome. Using these molecular markers of TL, we investigated the growth and differentiation potential of TL blasts in the presence of hematopoietic growth factors (HGFs). Interleukin-3, stem cell factor and granulocyte-macrophage colony-stimulating factor potently stimulated the growth of TL blast progenitors and induced differentiation towards basophil/mast cell lineages, whereas thrombopoietin induced differentiation towards megakaryocytes. GATA1s was expressed in TL blasts in all five patients examined but was down-regulated during differentiation induced by these HGFs, while full-length GATA1 was not expressed throughout the culture. GATA1 mutations were detected in TL blasts in four patients, including one patient with two distinct mutations. The cells of this patient exhibited identical and only mutated sequences both before and after culture with HGFs, confirming the leukemic cell origin of these differentiated cells. Erythroid differentiation of TL blasts was not evident with any HGFs. These data indicate that TL blasts have the potential to grow and differentiate towards particular hematopoietic lineages in the presence of specific HGFs and that the down-regulation of GATA1s might be involved in blast cell differentiation.
INFECTIOUS DISEASES - INFECCIONES
TÍTULO / TITLE:
- Down syndrome and streptococcus group A disease in hospitalized children.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Acta Paediatr. 2009 Dec 9.
AUTORES / AUTHORS:
- Megged O; Schlesinger Y
INSTITUCIÓN / INSTITUTION:
- Department of Pediatrics and Infectious Diseases Unit, Shaare Zedek Medical Center, Jerusalem, affiliated with the Hadassah-Hebrew University Medical School, Jerusalem, Israel.
RESUMEN / SUMMARY:
-
TÍTULO / TITLE:
- Both normal memory counts and decreased naive cells favor intrinsic defect over early senescence of Down syndrome T-lymphocytes.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Pediatr Res. 2010 Jan 21.
AUTORES / AUTHORS:
- Kusters MA; Gemen EF; Verstegen RH; Wever PC; de Vries E
INSTITUCIÓN / INSTITUTION:
- Department of Pediatrics [M.A.A.K., R.H.J.V., E.V.], Department of Clinical Chemistry and Hematology E.F.A.G.], Department of Medical Microbiology and Infection Control [P.C.W.] Jeroen Bosch Hospital, s-Hertogenbosch, 5200ME, The Netherland
RESUMEN / SUMMARY:
- Due to their increased malignancies, autoimmune diseases, and infections, patients with Down syndrome (DS) show features of immunodeficiency. The DS thymus and T-lymphocyte subsets have indeed proven to be different, and this has been interpreted as precocious aging. Our study on T-lymphocyte subpopulations in DS shows that the normal expansion of naive helper (CD4+CD45RA+) and cytotoxic (CD8+CD45RA+CD27+) T-lymphocytes is lacking in the first years of life; this is more logically explainable with an intrinsic T-lymphocyte defect. Furthermore, memory cell numbers are not different from age-matched controls (AMC), which does not support the hypothesis of precocious aging. Although the absolute numbers of T-lymphocyte subpopulations approach AMC levels towards adulthood, the persistent clinical problems suggest these cells may not function optimally. However, the clinical picture does not fit severe T-lymphocyte deficiency. The latter concept is also supported by our finding that cytomegalovirus (CMV)-seropositive DS children show similar numbers of terminally differentiated cytotoxic T-lymphocytes when compared to healthy children, not increased numbers as are seen in immunocompromised hosts.
TÍTULO / TITLE:
- Down syndrome B-lymphocyte subpopulations, intrinsic defect or decreased T-lymphocyte help.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Pediatr Res. 2010 Jan 21.
AUTORES / AUTHORS:
- Verstegen RH; Kusters MA; Gemen EF; de Vries E
INSTITUCIÓN / INSTITUTION:
- Department of Pediatrics [R.H.J.V., M.A.A.K., E.V.], Department of Clinical Chemistry and Hematology [E.F.A.G.], Jeroen Bosch Hospital, ‘s-Hertogenbosch, 5200 ME, The Netherlands.
RESUMEN / SUMMARY:
- Down Syndrome (DS) is known for increased incidence of respiratory infections and autoimmune diseases, indicating impaired immunity. Until now, attention has been mainly focused on T-lymphocytes. Therefore, we determined B-lymphocyte subpopulations in 95 DS-children compared to 33 age-matched controls. DS serum immunoglobulin levels were compared to 962 non-DS-children with recurrent infections. The results were combined with clinical data. Transitional and naive B-lymphocytes are profoundly decreased in the DS children. This could be caused by an intrinsic B-lymphocyte defect resulting in (partial) failure of B-lymphocyte generation, decreased antigen-induced proliferation and/or increased apoptosis, or by decreased proliferation due to deficient T-lymphocyte help, or a combination of these. The decreased CD27, CD21 and CD23 cells are reminiscent of Common Variable Immunodeficiency and suggestive of disturbed peripheral B-lymphocyte maturation. Immunoglobulin levels in DS are abnormal - as has been described before - and different from non-DS children with recurrent infections. We conclude that the humoral immune system is abnormal in DS, but could not find a relation between B-lymphocyte subsets, immunoglobulins and clinical features of the DS children in our cohort, nor could we answer the question whether DS lymphocytes are truly intrinsically deficient, or could all findings be explained by deficient T-lymphocyte help.
MOLECULAR BIOLOGY/BIOCHEMISTRY - BIOLOGÍA MOLECULAR/BIOQUÍMICA
TÍTULO / TITLE:
- The E3 ligase TTC3 facilitates ubiquitination and degradation of phosphorylated Akt.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Dev Cell. 2009 Dec;17(6):800-10.
AUTORES / AUTHORS:
- Suizu F; Hiramuki Y; Okumura F; Matsuda M; Okumura AJ; Hirata N; Narita M; Kohno T; Yokota J; Bohgaki M; Obuse C; Hatakeyama S; Obata T; Noguchi M
INSTITUCIÓN / INSTITUTION:
- Division of Cancer Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
RESUMEN / SUMMARY:
- The serine threonine kinase Akt is a core survival factor that underlies a variety of human diseases. Although regulatory phosphorylation and dephosphorylation have been well documented, the other posttranslational mechanisms that modulate Akt activity remain unclear. We show here that tetratricopeptide repeat domain 3 (TTC3) is an E3 ligase that interacts with Akt. TTC3 contains a canonical RING finger motif, a pair of tetratricopeptide motifs, a putative Akt phosphorylation site, and nuclear localization signals, and is encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. Moreover, DS cells exhibit elevated TTC3 expression, reduced phosphorylated Akt, and accumulation in the G(2)M phase, which can be reversed by TTC3 siRNA or Myr-Akt. Thus, interaction between TTC3 and Akt may contribute to the clinical symptoms of DS.
TÍTULO / TITLE:
- Integrative genomics identifies DSCR1 (RCAN1) as a novel NFAT-dependent mediator of phenotypic modulation in vascular smooth muscle cells
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- HUMAN MOLECULAR GENETICS, 19 (3): 468-479 FEB 1 2010
AUTORES / AUTHORS:
- Lee, MY; Garvey, SM; Baras, AS; Lemmon, JA; Gomez, MF; Bortz, PDS; Daum, G; LeBoeuf, RC; Wamhoff, BR
RESUMEN / SUMMARY:
- Vascular smooth muscle cells (SMCs) display remarkable phenotypic plasticity in response to environmental cues. The nuclear factor of activated T-cells (NFAT) family of transcription factors plays a critical role in vascular pathology. However, known functional NFAT gene targets in vascular SMCs are currently limited. Publicly available whole-genome expression array data sets were analyzed to identify differentially expressed genes in human, mouse and rat SMCs. Comparison between vehicle and phenotypic modulatory stimuli identified 63 species-conserved, upregulated genes. Integration of the 63 upregulated genes with an in silico NFAT-ome (a species-conserved list of gene promoters containing at least one NFAT binding site) identified 18 putative NFAT-dependent genes. Further intersection of these 18 potential NFAT target genes with a mouse in vivo vascular injury microarray identified four putative NFAT-dependent, injury-responsive genes. In vitro validations substantiate! d the NFAT-dependent role of Cyclooxygenase 2 (COX2/PTGS2) in SMC phenotypic modulation and uncovered Down Syndrome Candidate Region 1 (DSCR1/RCAN1) as a novel NFAT target gene in SMCs. We show that induction of DSCR1 inhibits calcineurin/NFAT signaling through a negative feedback mechanism; DSCR1 overexpression attenuates NFAT transcriptional activity and COX2 protein expression, whereas knockdown of endogenous DSCR1 enhances NFAT transcriptional activity. Our integrative genomics approach illustrates how the combination of publicly available gene expression arrays, computational databases and empirical research methods can answer specific questions in any cell type for a transcriptional network of interest. Herein, we report DSCR1 as a novel NFAT-dependent, injury-inducible, early gene that may serve to negatively regulate SMC phenotypic switching.
TÍTULO / TITLE:
- Down syndrome fibroblasts and mouse Prep1-overexpressing cells display increased sensitivity to genotoxic stress.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Nucleic Acids Res. 2010 Jan 27.
AUTORES / AUTHORS:
- Micali N; Longobardi E; Iotti G; Ferrai C; Castagnaro L; Ricciardi M; Blasi F; Crippa MP
INSTITUCIÓN / INSTITUTION:
- Laboratory of Molecular Dynamics of the Nucleus, Division of Genetics and Cell Biology, S. Raffaele Scientific Institute, via Olgettina 60, Milan 20132, IFOM (Fondazione Istituto FIRC di Oncologia Molecolare), via Adamello 16, Milan 20139,
RESUMEN / SUMMARY:
- PREP1 (PKNOX1) maps in the Down syndrome (DS) critical region of chromosome 21, is overexpressed in some DS tissues and might be involved in the DS phenotype. By using fibroblasts from DS patients and by overexpressing Prep1 in F9 teratocarcinoma and Prep1(i/i) MEF to single out the role of the protein, we report that excess Prep1 increases the sensitivity of cells to genotoxic stress and the extent of the apoptosis directly correlates with the level of Prep1. The apoptotic response of Prep1-overexpressing cells is mediated by the pro-apoptotic p53 protein that we show is a direct target of Prep1, as its depletion reverts the apoptotic phenotype. The induction of p53 overcomes the anti-apoptotic role of Bcl-X(L), previously shown to be also a Prep1 target, the levels of which are increased in Prep1-overexpressing cells as well. Our results provide a rationale for the involvement of PREP1 in the apoptotic phenotype of DS tissues and indicate that differences in Prep1 level can have drastic effects.
TÍTULO / TITLE:
- Apoptosis is directly related to intracellular amyloid accumulation in a cell line derived from the cerebral cortex of a trisomy 16 mouse, an animal model of Down syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Neurosci Lett. 2009 Dec 30.
AUTORES / AUTHORS:
- Arriagada C; Bustamante M; Atwater I; Rojas E; Caviedes R; Caviedes P
INSTITUCIÓN / INSTITUTION:
- ICBM, Program of Anatomy and Developmental Biology, Faculty of Medicine, University of Chile, Independencia 1027, Santiago, Chile.
RESUMEN / SUMMARY:
- Human Down syndrome (DS) represents the most frequent cause of mental retardation associated to a genetic condition. DS also exhibits a characteristic early onset of neuropathology indistinguishable from that observed in Alzheimer’s disease (AD), namely the deposition of the beta-amyloid peptide. Early endosomal dysfunction has been described in individuals with DS and AD, suggesting an important role of this subcellular compartment in the onset and progression of the pathology. On the other hand, cholesterol activates the amyloidogenic processing pathway for the amyloid precursor protein, and the lipoprotein receptor-related peptide interacts with the beta-amyloid peptide. In the present work, using cell lines derived from the cortex of both normal and trisomy 16 mice (Ts16), an animal model of DS, we showed that the application of exogenous beta-amyloid has cytotoxic effects, expressed in decreased viability and increased apoptosis. Supplementation of the culture media with cholesterol associated to lipoprotein increased cell viability in both cell lines, but apoptosis decreased only in the normal cell line. Further, intracellular beta-amyloid content was elevated in trisomic cells following cholesterol treatment, with higher values in the trisomic cell line. Immunocytochemical detection showed intracellular accumulation of exogenous beta-amyloid in Rab4-positive compartments, which are known to be associated to endosomal recycling. The results suggest that the intracellular beta-amyloid pool plays a central role in apoptosis-mediated cell death in the trisomic condition.
TÍTULO / TITLE:
- Molecular basis of pharmacotherapies for cognition in Down syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Trends Pharmacol Sci. 2009 Dec 4.
AUTORES / AUTHORS:
- Gardiner KJ
INSTITUCIÓN / INSTITUTION:
- Department of Pediatrics, Intellectual and Developmental Disability Research Center, Human Medical Genetics and Neuroscience Programs, University of Colorado Denver, 12800 E 19(th) Avenue, Aurora, Colorado, 80045, USA.
RESUMEN / SUMMARY:
- Intellectual disability in Down syndrome (DS) ranges from low normal to severely impaired and has a significant impact on the quality-of-life of the individuals affected and their families. Because the incidence of DS remains at approximately 1 in 700 live births and the lifespan is now >50 years, development of pharmacotherapies for cognitive deficits is an important goal. DS is due to an extra copy of human chromosome 21 and has often been considered too complex a genetic abnormality to be amenable to intervention. However, recent successes in rescuing learning/memory impairments in a mouse model of DS suggest that this negative outlook may not be justified. In this contribution, we first review the DS phenotype, chromosome 21 gene content and mouse models. We then discuss recent successes and the remaining challenges in the identification of targets for and preclinical evaluation of potential therapeutics.
TÍTULO / TITLE:
- Spinal myxopapillary ependymoma with Down syndrome: exploring an unusual association.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- J Pediatr Hematol Oncol. 2010 Jan;32(1):e38-41.
AUTORES / AUTHORS:
- Biswas A; Puri T; Goyal S; Kumar S; Sharma A; Paliwal P; Suri V; Jain A; Julka PK; Rath GK
INSTITUCIÓN / INSTITUTION:
- Department of *Radiotherapy, All India Institute of Medical Sciences, St Stephen’s Hospital, New Delhi, India.
RESUMEN / SUMMARY:
- SUMMARY: In patients with Down syndrome, cancers like leukemia and testicular tumors are frequent, but association with central nervous system tumors is rare. Only 1 case of ependymoma has been observed as an incidental autopsy finding in a 19-week-old female fetus. We herein report the second case of ependymoma and the fifth case of spinal tumor occurring in association with Down syndrome. We have also attempted to elucidate the various mechanisms of tumorigenesis implicated in this multiple malformation syndrome. A 13-year-old girl with Down syndrome presented with progressively increasing paraparesis and neurogenic bladder. Magnetic resonance imaging of dorsolumbar spine revealed an intramedullary mass (L1 to L5 level). The patient underwent near total excision of tumor with postoperative histopathology showing myxopapillary ependymoma. Karyotyping showed classic Down syndrome with trisomy 21. Postoperative irradiation (45 Gy in 25 fractions over 5 wk followed by boost up to 55 Gy) was subsequently delivered. One year after the completion of the tumor-directed therapy, the patient is in radiologic complete remission, with improved power in both lower limbs. Association of ependymoma with Down syndrome is a rarity, which at best, can be explained as a chance phenomenon.
TÍTULO / TITLE:
- Misleading appearance of atlantoaxial diastasis in Down syndrome: os odontoideum.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- JBR-BTR. 2009 Sep-Oct;92(5):261.
AUTORES / AUTHORS:
- Hericord O; Bosschaert P; Menten R; Dembour G
INSTITUCIÓN / INSTITUTION:
- Service de Radiologie, Clinique Saint Pierre, Ottignies.
RESUMEN / SUMMARY:
-
TÍTULO / TITLE:
- Single Stage Reduction and Stabilization of Basilar Invagination After Failed Prior Fusion Surgery in Children With Down’s Syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Spine (Phila Pa 1976). 2010 Jan 27.
AUTORES / AUTHORS:
- Hedequist D; Bekelis K; Emans J; Proctor MR
INSTITUCIÓN / INSTITUTION:
- From the *Department of Orthopedic Surgery, Children’s Hospital Boston, Boston, MA; daggerDepartment of Neurosurgery, Dartmouth Medical School, Hanover, NH; and double daggerDepartment of Neurosurgery, Children’s Hospital Boston, Boston, MA
RESUMEN / SUMMARY:
- STUDY DESIGN.: We describe an innovative single-stage reduction and stabilization technique using modern cervical instrumentation. OBJECTIVE.: We hypothesis modern instrumentation has made more aggressive surgical corrections possible and has reduced the need for transoral resection of the odontoid and traction reduction in children with basilar invagination. SUMMARY OF BACKGROUND DATA.: Craniocervical junction abnormalities, including atlantoaxial instability and progressive basilar invagination, are relatively common phenomenon in Down’s syndrome patients, and can lead to chronic progressive neurologic deficits, catastrophic injury, and death. This patient population also can be a difficult one in which to perform successful stabilization and fusion. METHODS.: We reviewed the records and films on 2 children with Down’s syndrome and atlantoaxial instability who had undergone prior occipital-cervical fusion and then presented with symptomatic progressive basilar invagination due to atlantoaxial displacement. In both cases, the children had progressive symptoms of spinal cord and brain stem compression. Multiple approaches for surgical correction, including preoperative traction and transoral odontoid resection, were considered, but ultimately it was elected to perform a single stage posterior operation. In both patients, we performed fusion takedown, intraoperative realignment with reduction of the basilar invagination, and stabilization using modern occipito-cervical instrumentation. RESULTS.: In both children, excellent cranio-cervical realignment was achieved; along with successful fusion and improvement in clinical symptoms. CONCLUSION.: In this article we will discuss the clinical cases and review the background of craniocervical junction abnormalities in Down’s syndrome patients. We hypothesis modern instrumentation has made more aggressive surgical corrections possible and has reduced the need for transoral resection of the odontoid and traction reduction in children with basilar invagination.
TÍTULO / TITLE:
- Walking economy of adults with down syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Int J Sports Med. 2010 Jan;31(1):10-5. Epub 2009 Dec 22.
AUTORES / AUTHORS:
- Mendonca GV; Pereira FD; Morato PP; Fernhall B
INSTITUCIÓN / INSTITUTION:
- Human Kinetics Faculty, Human Kinetics, Lisboa, Portugal.
gvmendonca@gmail.com
RESUMEN / SUMMARY:
- This study intended to investigate walking economy (WE) in response to different treadmill speeds and grades in adults with Down syndrome (DS) and in non-disabled controls. Eighteen participants (14 males; 4 females) with DS (33.6+/-7.6 years) and 16 non-disabled (12 males, 4 females) controls (33.3+/-8.0 years) performed submaximal (2.5 km . h (-1) and 4 km . h (-1) at 0% grade; 4 km . h (-1) at 2.5% and 5% grade, for 5 min each) and maximal treadmill tests with metabolic and heart rate measurements. Oxygen uptake (VO(2)) was not different between groups at rest or during the slowest treadmill speed. However, at faster speeds and increased grades, adults with DS presented lower WE than controls (p<0.0001). Subsequent analyses revealed that, despite showing higher delta VO(2) response to the selected speed increments (p<0.0001), individuals with DS produced similar VO(2) increase as controls to grade variations. Therefore, adults with DS exhibit lower WE than non-disabled controls at a speed faster than their preferred walking speed. Additionally, in comparison to controls, individuals with DS show a greater change in energy expenditure with a change in walking speed. In conclusion, lower WE in individuals with DS is mainly related to their inability to adapt efficiently to positive variations in walking speed.
TÍTULO / TITLE:
- Effect of Treadmill Training and Supramalleolar Orthosis Use on Motor Skill Development in Infants With Down Syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Phys Ther. 2010 Jan 14.
AUTORES / AUTHORS:
- Looper J; Ulrich DA
INSTITUCIÓN / INSTITUTION:
- Physical Therapy Program, University of Puget Sound, 1500 N Warner St #1070, Tacoma, WA 98416-1070 (USA).
RESUMEN / SUMMARY:
- Background Children with Down syndrome (DS) often display delayed onset of independent walking. Treadmill training is an effective intervention that leads to an earlier walking onset. In addition, orthoses often are provided to infants with DS to increase stability and promote earlier independent walking. However, this early use of orthoses has not been scientifically verified in infants with DS. Objective The purpose of this study was to provide insight into the developmental outcomes of early orthosis use in combination with treadmill training in infants with DS compared with treadmill training alone. Design This study was a randomized controlled trial. Setting This study was conducted in participants’ homes and in the motor development laboratory. Participants and Intervention Seventeen infants with DS entered the study when they could pull themselves to a standing position. They were randomly assigned to either a control group (which received treadmill training) or an experimental group (which received treadmill training and orthoses). During monthly visits to the infants’ homes, 3 minutes of treadmill stepping was recorded and each child’s motor development skills were tested. The treadmill training ended once the child took 3 independent steps. One month following walking onset, developmental tests were readministered. Measurements The Gross Motor Function Measure (GMFM) was used to test motor skill development. RESULTS: /b> The average (SD) time in the study was 268 (88) days for the control group and 206 (109) days for the experimental group. All infants showed significantly increased GMFM scores over time. At 1 month of walking experience, the control group had higher GMFM scores than the experimental group, with higher standing and walking, running, and jumping subscale scores. Limitations Limitations of this study included a small sample of convenience, a statistical model that may have reduced validity at the tail end, and a lack of blinding in the GMFM scorer. CONCLUSIONS:/b> Orthoses may have a detrimental effect on overall gross motor skill development.
TÍTULO / TITLE:
- Gait analysis and cerebral volumes in Down’s syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Funct Neurol. 2009 Jul-Sep;24(3):147-52.
AUTORES / AUTHORS:
- Rigoldi C; Galli M; Condoluci C; Carducci F; Onorati P; Albertini G
RESUMEN / SUMMARY:
- The aim of this study was to look for a relationship between cerebral volumes computed using a voxel-based morphometry algorithm and walking patterns in individuals with Down’s syndrome (DS), in order to investigate the origin of the motor problems in these subjects with a view to developing appropriate rehabilitation programmes. Nine children with DS underwent a gait analysis (GA) protocol that used a 3D motion analysis system, force plates and a video system, and magnetic resonance imaging (MRI). Analysis of GA graphs allowed a series of parameters to be defined and computed in order to quantify gait patterns. By combining some of the parameters it was possible to obtain a 3D description of gait in terms of distance from normal values. Finally, the results of cerebral volume analysis were compared with the gait patterns found. A strong relationship emerged between cerebellar vermis volume reduction and quality of gait and also between grey matter volume reduction of some cerebral areas and asymmetrical gait. An evaluation of high-level motor deficits, reflected in a lack or partial lack of proximal functions, is important in order to define a correct rehabilitation programme.
PRENATAL DIAGNOSIS - DIAGNÓSTICO
TÍTULO / TITLE:
- Placental growth hormone and growth hormone binding protein are first trimester maternal serum markers of Down syndrome
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- PRENATAL DIAGNOSIS, 29 (13): 1249-1255 DEC 2009
AUTORES / AUTHORS:
- Christiansen, M
RESUMEN / SUMMARY:
- Background Placental growth hormone (PGH) is synthesised by the placenta, and its function is modulated by growth hormone binding protein (GHBP). The potential of PGH and GHBP as maternal serum screening markers for Down syndrome (DS) was examined.
Materials and methods Maternal serum concentrations of PGH and GHBP were determined by ELISA in 74 DS and 261 control pregnancies in gestational week 8(+0) to 13(+4). Log(10) MoM distributions of the markers were established. The performance of DS screening was estimated by Monte Carlo simulation.
Results PGH log(10) MoM (SD) was decreased (p < 0.001) to -0.201 (0.373) and GHBP log(10) MoM to -0.116 (0.265) (p = 0.04), in DS pregnancies (it = 34) in week 8(+0) to 10(+0). In week 10(+1) to 13(+4), neither PGH (p = 0.16) nor GHBP (p = 0.13) was reduced in DS pregnancies. The detection rate (DR) for PGH in screening for DS in week 8(+0) to 10(+0) was 39% for a false positive rate (FPR) of 5%; increasing to 72% in combination with PAPP-A + hCG beta. PGH + GHBP in combination with PAPP-A + hCG beta + nuchal translucency (NT) (CUB test) had a DR of 91% compared with 80% for the CUB test.
Conclusion PGH and GHBP are early first trimester maternal serum markers for DS [Correction made here after initial online publication]. Copyright (C) 2009 John Wiley & Sons, Ltd.
TÍTULO / TITLE:
- Comparison of first trimester contingent screening strategies for Down syndrome.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Ultrasound Obstet Gynecol. 2010 Jan 5.
AUTORES / AUTHORS:
- Sahota DS; Leung TY; Chan LW; Law LW; Fung TY; Chen M; Lau TK
INSTITUCIÓN / INSTITUTION:
- Department of Obstetrics and Gynaecology Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
RESUMEN / SUMMARY:
- OBJECTIVE:: To assess the relative performance of a multi-stage first trimester screening protocol for fetal Down syndrome. METHODS:: 10,767 women whom underwent combined ultrasound and biochemistry (BC) screening in the first trimester were re-analysed using a contingent model approach. Amongst the 10,854 fetuses with known outcome, 32 had Down syndrome and 10,590 were unaffected. pregnancy. Nuchal Transluceny (NT), BC and combined (NT+BC) gestational age specific risks were calculated for each individual using the Fetal Medicine Foundation risk calculation algorithms (Mixture Model and Biochemistry). Individual patients were categorised as either ‘Low’, ‘High’ or ‘Intermediate’ risk according to one of the following three strategies. In ‘Strategy-NTBC’ initial screening was performed using both the NT and BC. In ‘Strategy-BC’ initial screening was undertaken using maternal serum markers followed by NT assessment in those with an ‘Intermediate’ risk (1:51< Risk
TÍTULO / TITLE:
- Trisomy 18 and 13 screening: consequences for the Dutch Down syndrome screening programme.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Prenat Diagn. 2010 Jan 28.
AUTORES / AUTHORS:
- Koster MP; Stoutenbeek P; Visser GH; Schielen PC
INSTITUCIÓN / INSTITUTION:
- Diagnostic Laboratory for Infectious Diseases and Perinatal Screening, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
RESUMEN / SUMMARY:
-
TÍTULO / TITLE:
- Discovery of novel serum biomarkers for prenatal Down syndrome screening by integrative data mining.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- PLoS One. 2009 Nov 24;4(11):e8010.
AUTORES / AUTHORS:
- Pennings JL; Koster MP; Rodenburg W; Schielen PC; de Vries A
INSTITUCIÓN / INSTITUTION:
- Laboratory for Health Protection Research (GBO), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
Jeroen.Pennings@rivm.nl
RESUMEN / SUMMARY:
- BACKGROUND: To facilitate the experimental search for novel maternal serum biomarkers in prenatal Down Syndrome screening, we aimed to create a set of candidate biomarkers using a data mining approach. METHODOLOGY/PRINCIPAL FINDINGS: Because current screening markers are derived from either fetal liver or placental trophoblasts, we reasoned that new biomarkers can primarily be found to be derived from these two tissues. By applying a three-stage filtering strategy on publicly available data from different sources, we identified 49 potential blood-detectable protein biomarkers. Our set contains three biomarkers that are currently widely used in either first- or second-trimester screening (AFP, PAPP-A and fbeta-hCG), as well as ten other proteins that are or have been examined as prenatal serum markers. This supports the effectiveness of our strategy and indicates the set contains other markers potentially applicable for screening. CONCLUSIONS/SIGNIFICANCE: We anticipate the set will help support further experimental studies for the identification of new Down Syndrome screening markers in maternal blood.
TÍTULO / TITLE:
- Synergy of Total PLAC4 RNA Concentration and Measurement of the RNA Single-Nucleotide Polymorphism Allelic Ratio for the Noninvasive Prenatal Detection of Trisomy 21
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- CLINICAL CHEMISTRY, 56 (1): 73-81 JAN 2010
AUTORES / AUTHORS:
- Tsui, NBY; Akolekar, R; Chiu, RWK; Chow, KCK; Leung, TY; Lau, TK; Nicolaides, KH; Lo, YMD
RESUMEN / SUMMARY:
- BACKGROUND: Maternal plasma mRNA encoded by the PLAC4 gene (placenta-specific 4), which is transcribed from chromosome 21 in placental cells, is a potential marker for the noninvasive assessment of chromosome 21 dosage in the fetus. We evaluated the diagnostic sensitivities and specificities of 2 trisomy 21-screening approaches that use maternal plasma PLAC4 mRNA.
METHODS: We studied maternal plasma samples from 153 pregnant women carrying euploid and trisomy 21 fetuses. For the samples in which the fetuses were heterozygous for the studied PLAC4 single-nucleotide polymorphism (SNP), we measured the ratio between 2 alleles of the SNP in maternal plasma PLAC4 mRNA (RNA-SNP) by mass spectrometric (MS) and digital PCR methods. For pregnancies involving fetuses homozygous for the SNP, we quantified the total PLAC4 mRNA concentration in maternal plasma by real-time PCR and digital PCR.
RESULTS: For the RNA-SNP approach, we achieved a diagnostic sensitivity and specificity of 100% (95% CI, 40.2%-100%) and 89.7% (95% Cl, 78.8%-96.1%), respectively, for both the MS and the digital PCR methods. For the mRNA-quantification approach, the areas under the ROC curves were 0.859 (95% Cl, 0.741-0.903) and 0.833 (95% Cl, 0.770-0.923) for plasma PLAC4 mRNA concentrations measured by the real-time PCR and the digital PCR methods, respectively.
CONCLUSIONs: For prenatal screening of trisomy 21, the quantification of the total PLAC4 mRNA concentration can be used in a synergistic manner with the RNA-SNP allelic ratio approach to increase the Population coverage of cases in which diagnostic information can be obtained. (C) 2009 American Association for Clinical Chemistry
TÍTULO / TITLE:
- Noninvasive Prenatal Detection of Trisomy 21 by an Epigenetic-Genetic Chromosome-Dosage Approach
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- CLINICAL CHEMISTRY, 56 (1): 90-98 JAN 2010
AUTORES / AUTHORS:
- Tong, YK; Jin, SN; Chiu, RWK; Ding, CM; Chan, KCA; Leung, TY; Yu, L; Lau, TK; Lo, YMD
RESUMEN / SUMMARY:
- BACKGROUND: The use of fetal DNA in maternal plasma for noninvasive prenatal diagnosis of trisomy 21 (T21) is an actively researched area. We propose a novel method of T21 detection that combines fetal-specific epigenetic and genetic markers.
METHODS: We used combined bisulfite restriction analysis to search for fetal DNA markers on chromosome 21 that were differentially methylated in the placenta and maternal blood cells and confirmed any target locus with bisulfite sequencing. We then used methylation-sensitive restriction endonuclease digestion followed by microfluidics digital PCR analysis to investigate the identified marker. Chromosome-dosage analysis was performed by comparing the dosage of this epigenetic marker with that of the ZFY (zinc finger protein, Y-linked) gene on chromosome Y.
RESULTS: The putative promoter of the HLCS (holocarboxylase synthetase) gene was hypermethylated in the placenta and hypomethylated in maternal blood cells. A chromosome-dosage comparison of the hypermethylated HLCS and ZFY loci could distinguish samples of T21 and euploid placental DNA. Twenty-four maternal plasma samples from euploid pregnancies and 5 maternal plasma samples from T21. pregnancies were analyzed. All but I of the euploid samples were correctly classified.
CONCLUSIONS: The epigenetic-genetic chromosome-dosage approach is a new method for noninvasive prenatal detection of T21. The epigenetic part of the analysis can be applied to all pregnancies. Because the genetic part of the analysis uses paternally inherited, fetal-specific genetic markers that are abundant in the genome, broad population coverage should be readily achievable. This approach has the potential to become a generally usable technique for noninvasive prenatal diagnosis. (C) 2009 American Association for Clinical Chemistry
TÍTULO / TITLE:
- Umbilical Vein anomaly in fetuses with Down syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Ultrasound Obstet Gynecol. 2010 Jan 5.
AUTORES / AUTHORS:
- Achiron R; Gindes L; Gilboa Y; Weissmann-Brenner A; Berkenstadt M
INSTITUCIÓN / INSTITUTION:
- Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center, Tel Hashomer, Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Israel.
RESUMEN / SUMMARY:
- OBJECTIVES:: To describe the prevalence of abnormal umbilical vein (UV) anatomy in fetuses with Down syndrome. METHODS:: A retrospective survey of all fetuses diagnosed with Down syndrome after early second-trimester detailed fetal anomaly scan. All scans were performed at a single tertiary academic center. The detailed fetal anomaly scan was performed in all cases between 12 and 16 weeks’ gestation, using either a transvaginal multifrequency 6-12 MHz probe, or transabdominal 4-8MHz probes. Fetal umbilical venous system evaluation is an integral part of the routine antenatal sonographic examination in our unit. RESULTS:: During a study period of 24 months, 37 fetuses had a genetic diagnosis of Down syndrome. In four (11%) detailed early anomaly scan revealed that the UV was connected to the hepatic portion of the inferior vena cava (IVC) at a position lower than its usual site. The average gestational age at diagnosis was 13.4 weeks (range, 11-15 weeks). Three of the four fetuses had a nuchal translucency thickness between 3 and 4 mm. In one fetus we observed an additional finding of significant tricuspid regurgitation. Another fetus had normal nuchal thickness; however, a common atrioventricular valve and umbilical cord hernia were present. During the same period three of 2500 (0.12%) fetuses with normal karyotype demonstrated similar anomalous insertion of the Umbilical vein directly into the IVC creating a portocaval shunt. All three had a normal Doppler flow in the Portocaval shunt. The odds ratio for abnormal umbilico-portal system in Down syndrome compared with the normal population was 107.4 (95% CI;19.25-637.1). CONCLUSIONS:: Fetuses with Down syndrome demonstrated an increased prevalence of an abnormal connection of the UV to the IVC.
TÍTULO / TITLE:
- Maternal serum screening marker levels in women with a previous aneuploidy pregnancy
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- PRENATAL DIAGNOSIS, 29 (13): 1242-1243 DEC 2009
AUTORES / AUTHORS:
- Spencer, K; Staboulidou, I; Cruz, JD; Karagiannis, G; Nicolaides, KH
RESUMEN / SUMMARY:
- Objective To re-evaluate in a larger cohort of patients if the maternal serum biochemical markers used in first trimester aneuploidy screening have the same marker distributions in pregnancies with a previous history of aneuploidy compared with those that have no previous history.
Methods Information related to previous pregnancy history is routinely recorded as part of first trimester screening in three centres King George, Kings College and Fetal Medicine Centre, London. From the database, records were extracted for women who had a previous pregnancy diagnosed with ttisomies 13, 18 or 21. For each woman with a previous aneuploidy, five unaffected pregnancies in women of the same maternal age and with no previous aneuploidy pregnancy were selected as controls. A comparison was made between the marker distributions for pregnancy associated plasma protein-A (PAPP-A) and free beta-human chronic gonadotrophin (beta-hCG) amongst the cases and controls using nonparametric statistical tests.
Results A series of 8240 controls were compared against group of 1032 cases with a previous trisomy 21, 293 with a previous trisomy 18 and 158 with a previous trisomy 13. Cases with multiple previous trisomies were excluded. There were no significant differences in the level of free beta-hCG; however, in cases of trisomy 21 and trisomy 13 the levels of PAPP-A were increased by 5 and 16%, respectively.
Conclusion Risk calculation algorithms may need to take account of the increased PAPP-A levels in women with a previous trisomy 21 or trisomy 13, Copyright (C) 2009 John Wiley & Sons, Ltd.
TÍTULO / TITLE:
- Nasal bone in prenatal trisomy 21 screening.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Obstet Gynecol Surv. 2010 Jan;65(1):46-52.
AUTORES / AUTHORS:
- Shanks A; Odibo A
INSTITUCIÓN / INSTITUTION:
- Maternal-Fetal Medicine, Washington University in St. Louis, St. Louis, MO, USA.
shanksa@wudosis.wustl.edu
RESUMEN / SUMMARY:
- The definitive diagnosis of fetal chromosomal abnormalities is only accomplished through tests that sample fetal tissue. These procedures—amniocentesis, chorionic villus sampling and cordocentesis—are invasive and carry with them the risks of bleeding, rupture of membranes, and even pregnancy loss. Current recommendations from the American College of Obstetricians and Gynecologists state that all women should be offered screening, regardless of maternal age. However, the exact screening test to apply to pregnant women is still a matter of debate. The goal of any screening method should be high detection (sensitivity) at low screen positive rates. Recent attention has focused on additional ultrasound markers to potentially improve the detection rate. Given that mid-face hypoplasia and a flattened nose are characteristic features of Down syndrome, investigators have tried to utilize its prenatal appearance—or more specifically, its absence—to enhance the detection of trisomy 21 (T21). The purpose of this document is to review the data on the utility of the nasal bone as a marker for T21. Particular attention will focus on its use in the first trimester versus second trimester as well as future directions for its potential incorporation into screening strategies. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to relate the prenatal and postnatal nasal phenotypes for Down syndrome, identify the potential role and pitfalls of nasal bone characteristics in screening for Down syndrome, and describe 3 different methods to define fetal nasal bone hypoplasia.
TÍTULO / TITLE:
- First-trimester fetal nasal bone audit: evaluation of a novel method of image assessment
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- ULTRASOUND IN OBSTETRICS & GYNECOLOGY, 34 (6): 623-628 DEC 2009
AUTORES / AUTHORS:
- McLennan, A; Schluter, PJ; Pincham, V; Hyett, J
RESUMEN / SUMMARY:
- Objectives Absence of the nasal bone has been recognized to be a strong ultrasound marker for Down syndrome and its inclusion in combined first-trimester screening would increase the sensitivity and specificity of this test. We describe the development of a method of image scoring that should allow reliable assessment of practitioners submitting themselves to peer review for nasal bone imaging.
Methods Twenty sonographers submitted 20 images demonstrating the presence of the nasal bone for quality assurance audit. linage quality was compared with the criteria described by The Fetal Medicine Foundation. Three raters scored the images on four separate occasions. On the first two occasions all 400 images were assessed qualitatively and given a simple pass/fail score. On the third and fourth occasions, five images from each of the 20 sets were scored objectively for five criteria by each of the three raters, with a cut-off applied to the scores generated. The reliability of these image assessment techniques was compared statistically.
Results Through quantitative assessment, 84% of images were judged in the same manner by three raters on two separate occasions and in 94% of cases five of these six ratings drew the same conclusion. Rates of intrarater and inter-rater agreement were significantly better using quantitative rather than qualitative techniques.
Conclusions This study has shown that clearly defined assessment criteria together with a quantitative scoring method improve the reliability of expert peer review. The quantitative method is recommended as the basis for future nasal bone image audit. Copyright (C) 2009 ISUOG. Published by John Wiley & Sons, Ltd.
TÍTULO / TITLE:
- Placental protein 13 as a first trimester screening marker for aneuploidy
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- PRENATAL DIAGNOSIS, 29 (13): 1237-1241 DEC 2009
AUTORES / AUTHORS:
- Koster, MPH; Wortelboer, EJ; Cuckle, HS; Stoutenbeek, P; Visser, GHA; Schielen, PCJI
RESUMEN / SUMMARY:
- Objective To determine whether Placental Protein 13 (PP13) could be an additional marker in first trimester screening for aneuploidies.
Methods To evaluate differences in multiples of the gestation-specific normal median (MoMS), PP13 concentrations were measured in serum samples from Down syndrome, trisomy 18 and 13 affected pregnancies and euploid singleton pregnancies (four for each case matched for duration of storage, maternal weight and age).
Results The PP13 MoM in Down syndrome cases (n = 153) was 0.91 [not statistically significant from controls (n = 853); P = 0.06; Wilcoxon rank sum test, two-tail]. PP13 MoMs were decreased in trisomy 18 (n = 38-median MoM 0.64: P < 0.0001) and trisomy 13 cases (n = 23-median MoM 0.46; P < 0.0001). There was a slight upward trend in MoM values of the Down syndrome cases with gestational weeks. The PP13 MoM was significantly correlated with the pregnancy associated plasma protein-A MoM and the free beta-subunit of human chorion gonadotrophin (f beta-hCG) MoM.
Conclusion PP13 does not seem to be a good marker for Down syndrome. PP13 MoMs are, however, significantly lower in trisomy 18 and 13 pregnancies. The addition of PP13 to the current screening test could be valuable for improving the discrimination of aneuploid from euploid pregnancies.
TÍTULO / TITLE:
- Bedside estimation of Down syndrome risk from second-trimester ultrasound prenasal thickness.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Ultrasound Obstet Gynecol. 2009 Dec;34(6):629-33.
AUTORES / AUTHORS:
- Maymon R; Moskovitch M; Levinsohn-Tavor O; Weinraub Z; Herman A; Cuckle H
INSTITUCIÓN / INSTITUTION:
- Department of Obstetrics and Gynecology, Assaf Harofe Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Israel
intposgr@post.tau.ac.il
RESUMEN / SUMMARY:
- OBJECTIVES: To construct tables for ‘bedside’ estimation of Down syndrome risk based on maternal age and ultrasound prenasal thickness (PT) measurements. METHODS: Likelihood ratios were calculated using a log Gaussian model of the PT distribution in multiples of the gestational age-specific median (MoM). The model parameters were derived from 80 Down syndrome and 850 unaffected pregnancies scanned at 14-27 weeks; these data had been published previously, in three series, except for 18 Down syndrome and 119 affected pregnancies. The means were estimated as the median, and the SDs as the 10(th)-90(th) range divided by 2.563. RESULTS: A log Gaussian model fitted well the distribution of PT values in Down syndrome and unaffected pregnancies with medians of 1.31 MoM and 1.01 MoM, and log(10) SDs of 0.075 and 0.082, respectively. CONCLUSIONS: The tables provide a simple ‘bedside’ estimation of Down syndrome risk without the need for computerized software or complicated calculations. More prospective data on PT in combination with other first- and second-trimester screening markers are needed.
TÍTULO / TITLE:
- Maternal plasma levels of follistatin-related gene protein in the first trimester of pregnancies with Down syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Prenat Diagn. 2010 Jan 8.
AUTORES / AUTHORS:
- Miron P; Lambert J; Marcil A; Cowans NJ; Stamatopoulou A; Spencer K
INSTITUCIÓN / INSTITUTION:
- Department of Obstetrics and Gynaecology, Hopital Maisonneuve-Rosemont, Faculty of Medicine, Universite de Montreal, Montreal, Quebec, Canada.
RESUMEN / SUMMARY:
- OBJECTIVE: To determine maternal plasma levels of follistatin-related gene protein (FLRG) in the first trimester of pregnancy and assess its potential role as a marker for prenatal screening of Down syndrome. METHODS: Maternal plasma levels of FLRG were determined in 100 pregnant women with normal fetuses in their first trimester of pregnancy (i.e. 11th to 15th weeks). These results were compared with 20 cases with Down syndrome fetuses, taking into consideration clinical and demographic variables, such as maternal age, maternal weight, gestational age, smoking status and ethnicity. RESULTS: Maternal plasma median of FLRG in the normal population was 1.41 ng/mL with 95% confidence interval (CI) of 1.37-1.70 and interquartile range (IQR) of 0.88, during the 11th to 15th weeks of pregnancy. Maternal age and weight were the only variables significantly related to FLRG levels (p = 0.030 and 0.020, respectively). Only maternal and gestational ages were related to Down syndrome (p = 0.039 and 0.006, respectively). Maternal plasma levels of FLRG were not significantly different in the presence of Down syndrome fetuses compared to normal population (p = 0.63). CONCLUSION: FLRG can be successfully detected in maternal plasma in the first trimester of pregnancy. However, its levels are not significantly altered in the presence of Down syndrome fetuses.
TÍTULO / TITLE:
- Preimplantation genetic diagnosis (polar body biopsy) and trisomy 21.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Hum Reprod. 2010 Jan 26.
AUTORES / AUTHORS:
- Schippert C; Bloechle M; Marr S; Caliebe A; Siebert R; Hillemanns P; von Kaisenberg CS
INSTITUCIÓN / INSTITUTION:
- Department of Obstetrics, Gynecology and Reproductive Medicine, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
RESUMEN / SUMMARY:
-
TÍTULO / TITLE:
- Nasal Bone in Prenatal Trisomy 21 Screening
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- OBSTETRICAL & GYNECOLOGICAL SURVEY, 65 (1): 46-52 JAN 2010
AUTORES / AUTHORS:
- Shanks, A; Odibo, A
RESUMEN / SUMMARY:
- The definitive diagnosis of fetal chromosomal abnormalities is only accomplished through tests that sample fetal tissue. These procedures-amniocentesis, chorionic villus sampling and cordocentesis-are invasive and carry with them the risks of bleeding, rupture of membranes, and even pregnancy loss. Current recommendations from the American College of Obstetricians and Gynecologists state that all women should be offered screening, regardless of maternal age. However, the exact screening test to apply to pregnant women is still a matter of debate.
The goal of any screening method should be high detection (sensitivity) at low screen positive rates. Recent attention has focused on additional ultrasound markers to potentially improve the detection rate. Given that mid-face hypoplasia and a flattened nose are characteristic features of Down syndrome, investigators have tried to utilize its prenatal appearance-or more specifically, its absence-to enhance the detection of trisomy 21 (T21).
The purpose of this document is to review the data on the utility of the nasal bone as a marker for T21. Particular attention will focus on its use in the first trimester versus second trimester as well as future directions for its potential incorporation into screening strategies.
TÍTULO / TITLE:
- Iliac crest angle: a novel sonographic parameter for the prediction of Down syndrome risk during the second trimester of pregnancy.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Ultrasound Obstet Gynecol. 2009 Dec 15;35(2):163-171.
AUTORES / AUTHORS:
- Lee W; Balasubramaniam M; Yeo L; Hassan SS; Gotsch F; Kusanovic JP; Goncalves LF; Romero R
INSTITUCIÓN / INSTITUTION:
- Division of Fetal Imaging, Department of Obstetrics and Gynecology, William Beaumont Hospital, Royal Oak, MI, USA.
RESUMEN / SUMMARY:
- OBJECTIVES: To validate a new sonographic technique for the display and measurement of fetal iliac crest angle (ICA), and to determine the relative contribution of standardized fetal pelvic measurements for estimating risk of Down syndrome during the second trimester of pregnancy. METHODS: Three-dimensional ultrasonography of the fetal pelvis was performed during a second-trimester scan for genetic amniocentesis. A coronal view of the ‘virtual pelvis’ was obtained by applying a maximum intensity projection algorithm to visualize both iliac wings. Two different ICAs were measured from a coronal projection of the fetal pelvis (ICA-coronal 1 and ICA-coronal 2); the latter approach relied on using ischial tuberosities as reference landmarks. Next, a coronal projection of the fetal pelvis was rotated to demonstrate a rendered view of the axial fetal pelvis. Axial inner (ICA-inner), middle (ICA-middle) and outer (ICA-outer) ICAs were measured. The maximum anterior iliac distance measurement was defined as the widest separation between the most anterior points of the rendered iliac crests. The reproducibility of each ICA method was analyzed using Bland-Altman statistics. Simple and multiple logistic regression analysis determined the relative contribution of each parameter as a prenatal predictor of Down syndrome. RESULTS: Ninety-four normal fetuses and 19 fetuses with Down syndrome were examined. The ICA-middle and ICA-coronal 2 parameters were the most reproducible angle measurements. The mean +/- SD ICA-middle measurement for fetuses with Down syndrome was significantly greater than that for normal subjects (94.5 +/- 9.8 degrees vs. 83.1 +/- 6.5 degrees ; P < 0.001). The mean +/- SD ICA-coronal 2 angle measurement for fetuses with Down syndrome was slightly greater than that for normal subjects (57.9 +/- 5.5 degrees vs. 51.9 +/- 7.1 degrees ; P = 0.0014). A multiple logistic regression model including ICA-middle and ICA-coronal 2 provided a predictive ability of 88.1% based on the area under the receiver-operating characteristics curve. This combination had a sensitivity of 94.4% for a false-positive rate of 5% in the detection of Down syndrome. CONCLUSIONS: Standardized iliac crest measurements of the fetal pelvis can be used to identify some fetuses at risk for trisomy 21 during the second trimester of pregnancy.
TÍTULO / TITLE:
- Mitral valve-tricuspid valve distance as a sonographic marker of trisomy 21.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Ultrasound Obstet Gynecol. 2009 Dec 22;35(2):172-177.
AUTORES / AUTHORS:
- Grace D; Eggers P; Glantz JC; Ozcan T
INSTITUCIÓN / INSTITUTION:
- University of Rochester Medical Center, Rochester, New York, USA
RESUMEN / SUMMARY:
- OBJECTIVE: Pathologic studies suggest that a decreased mitral valve-tricuspid valve distance (MTD) is found in trisomy 21 fetuses without cardiac defects. We assessed the feasibility of using the MTD as a second-trimester sonographic marker for trisomy 21. METHODS: We performed a retrospective case-control study of all cases of trisomy 21 at our institution from 1998 to 2008. Cases without a prenatally identified cardiac defect and with adequate images from 15 to 26 weeks’ gestation were assessed. The distance between the medial insertions of the mitral and tricuspid valves (i.e. the MTD) onto the ventricular septum was obtained. We also obtained the MTD from normal controls during the study period. Multiple linear regression analysis was used to assess the effects of gestational age and trisomy 21 on MTD. Gestational age-specific percentiles and multiples of the median were calculated, and curves were fitted using linear regression analysis. RESULTS: We identified 57 trisomy 21 fetuses with a measurable MTD and compared these with 634 control fetuses. Multiple linear regression analysis revealed a positive correlation between MTD and gestational age and a negative correlation between trisomy 21 and MTD. Using a cut-off of the 5(th) percentile, the MTD detected 70% of trisomy 21 cases with a 3.8% false-positive rate in the controls. CONCLUSIONS: The MTD increases with gestational age and is lower in fetuses with trisomy 21. Twenty (35%) of the 57 cases had no sonographic marker of trisomy 21 except an MTD below the 5(th) percentile for gestational age. The MTD was a useful independent marker for trisomy 21 in the second trimester.
TÍTULO / TITLE:
- Do race-specific definitions of short long bones improve the detection of down syndrome on second-trimester genetic sonograms?
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- J Ultrasound Med. 2010 Feb;29(2):231-5.
AUTORES / AUTHORS:
- Harper LM; Gray D; Dicke J; Stamilio DM; Macones GA; Odibo AO
INSTITUCIÓN / INSTITUTION:
- Department of Obstetrics and Gynecology, Washington University, 660 S Euclid, Campus Box 8064, St Louis, MO 63110 USA.
harperl@wudosis.wustl.edu
RESUMEN / SUMMARY:
- OBJECTIVE: The purpose of this study was to determine whether the use of race-specific definitions of short femur and humerus lengths improves Down syndrome detection. METHODS: This was a retrospective cohort study over 16 years. For each self-reported maternal race (white, African American, Hispanic, and Asian), we evaluated the efficiency of Down syndrome detection using published race-specific formulas compared with a standard formula for short femur and humerus lengths (observed versus expected lengths < or =0.91 and < or =0.89, respectively). The sensitivity, specificity, and 95% confidence intervals for each parameter were compared. Screening performance was compared by areas under the receiver operating characteristic curves. RESULTS: Of 58,710 women, 209 (0.3%) had a diagnosis of a fetus with Down syndrome. Although the race-based formula increased sensitivity in each population, the increase was statistically significant only in the white population, whereas a decrease in specificity was statistically significant in all 4 populations, as denoted by nonoverlapping confidence intervals. The area under the receiver operating characteristic curve for the model using the race-specific definition of short femur length was 0.67 versus 0.65 compared with the standard definition, and for humerus length it was 0.70 versus 0.71. CONCLUSIONS: The use of race-based formulas for the determination of short femur and humerus lengths did not significantly improve the detection rates for Down syndrome.
TÍTULO / TITLE:
- Increased time-to-pregnancy and first trimester Down’s syndrome screening.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Hum Reprod. 2010 Feb;25(2):412-7. Epub 2009 Nov 26.
AUTORES / AUTHORS:
- Ranta JK; Raatikainen K; Romppanen J; Pulkki K; Heinonen S
INSTITUCIÓN / INSTITUTION:
- Eastern Finland Laboratory Centre and Institute of Clinical Medicine, Faculty of Medicine, University of Kuopio, P.O. Box 1700, 70211 Kuopio, Finland.
RESUMEN / SUMMARY:
- BACKGROUND: Time-to-pregnancy (TTP) is a clinical tool used to measure uterine receptivity and a couples’ fertility in spontaneously conceived pregnancies. The objective of this study was to examine the effects of TTP on first trimester Down’s syndrome (DS) markers in spontaneous, chromosomally normal pregnancies and to compare the results to those in IVF pregnancies. METHODS: A case-control study was conducted amongst patients attending a university hospital in Finland. During 2005-2007 data on pregnant women in Kuopio, with singleton pregnancies, routinely collected by the Department of Obstetrics and Gynaecology of Kuopio University Hospital and Eastern Finland Laboratory Centre were compiled. The data comprised information gathered in first trimester DS screening [age of the mother, serum hCG free beta subunit (fbeta-hCG) and pregnancy-associated plasma protein A (S-PAPP-A) levels and the nuchal translucency (NT) of the fetus], body mass index, method of conception [spontaneous or in vitro fertilization (IVF)], TTP (in spontaneous pregnancies), maternal chronic diseases, smoking habits of the mother, outcome of the pregnancy and prior pregnancy complications. Spontaneous pregnancies were classified into three groups by TTP: 0-12 months (the reference group, N = 1164), 13-24 months (N = 112) and > or = 25 months (N = 70). Screening data from IVF pregnancies (N = 39) were collected for comparison. The size of the total study population was 1385. RESULTS: The median/geometric mean multiple of median (MOM) of S-PAPP-A was significantly lower (P < 0.01) in women with a TTP over 25 months (0.89/0.83 MOM) and in the IVF group (0.95/0.84 MOM) compared with the reference group (1.01/1.03 MOM). However, first trimester S-fbeta-hCG and NT MOMs were not statistically different between the study groups. Consequently, the proportion of DS screening positives was significantly higher in women with TTP > or = 25 months (12.9 versus 2.1%), but not in the IVF group (2.6%). CONCLUSIONS: A TTP of over 2 years altered the levels of DS screening serum markers to levels similar to those observed in IVF pregnancies, with a decrease in PAPP-A levels compared with the reference group. These results raise the possibility that such changes could be related to subfertility rather than to the use of assisted reproductive technology.
TÍTULO / TITLE:
- How much do family physicians involve pregnant women in decisions about prenatal screening for Down syndrome?
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Prenat Diagn. 2009 Dec 10;30(2):115-121.
AUTORES / AUTHORS:
- Gagnon S; Labrecque M; Njoya M; Rousseau F; St-Jacques S; Legare F
INSTITUCIÓN / INSTITUTION:
- Centre de recherche du CHUQ-CRSFA, Quebec, Canada.
RESUMEN / SUMMARY:
- OBJECTIVE: To assess the extent to which family physicians (FPs) involve women in decisions about prenatal screening for Down syndrome. METHODS: Based on transcripts of consultations between 41 FPs and 128 women, two raters independently assessed clinician’s efforts to involve women in decisions about prenatal screening for Down syndrome using the French-language version of OPTION. Descriptive statistics of OPTION scores were calculated. Construct validity was assessed by performing a principal factor analysis and by measuring association with consultation duration and FPs sociodemograhics. Internal consistency was assessed with Cronbach’s alpha and inter-rater reliability with the intraclass correlation coefficient. RESULTS: The overall mean OPTION score was low: 19 +/- 7 (range = 0 [no involvement] to 100 [high involvement]). One factor accounted for 80% of the variance. Both internal consistency and inter-rater reliability were very good (Cronbach’s alpha = 0.73; ICC = 0.76). OPTION scores were lower for residents than for licensed FPs (17 +/- 5 vs 21 +/- 4; p = 0.02) and were positively associated with duration of consultation (r = 0.56; p < 0.001). CONCLUSION: Based on the French-language version of OPTION, which showed satisfactory psychometric properties, FPs studied put minimal efforts to involve women in decisions about prenatal screening for Down syndrome.
TÍTULO / TITLE:
- Contingent triple-screening for Down syndrome in the second trimester: a feasibility study in Mainland Chinese population.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Prenat Diagn. 2010 Jan;30(1):74-6.
AUTORES / AUTHORS:
- Xie Z; Lu S; Li H
INSTITUCIÓN / INSTITUTION:
- Women’s Hospital, School of Medicine, Zhejiang University, No. 2 Xueshi Road, Hangzhou, China.
RESUMEN / SUMMARY:
- OBJECTIVES: To explore the efficacy of contingent triple-screening for Down syndrome (DS), that is, performing triple-screening in pregnant women with DS risks between 1/270 and 1/1000 at routine double-screening, in a Mainland Chinese population. METHODS: Maternal serum concentrations of alpha fetoprotein (AFP), free-beta human chorionic gonadotropin (free beta-hCG), and unconjugated estriol (uE3) were measured by time-resolved fluoroimmunoassay in 24 double-screening false-negative (DSFN) and 322 double-screening true-negative (DSTN) pregnancies with DS risks between 1/270 and 1/1000 at routine double-screening performed at 15-20 weeks’ gestation. DS risk of each pregnancy was calculated by computer software. The detection rate (DR), false-positive rate (FPR), and costs of contingent triple-screening were calculated and compared with routine double-screening methods. RESULTS: Six of 24 DSFN and 3 of 322 DSTN were contingent triple-screening positive. Compared with routine double-screening, DR of contingent triple-screening increased by 10% (from 50% to 60%) without a significant increase of FPR (p > 0.05). When compared with routine triple-screening, uE3 costs in contingent triple-screening were reduced by more than 84.3%. CONCLUSIONS: Second-trimester maternal serum contingent triple-screening could be effective and suitable for prenatal care in Mainland China. Governments and Health Agencies of other developing countries may also find this strategy cost-effective.
TÍTULO / TITLE:
- ADAM 12 may be used to reduce the false positive rate of first trimester combined screening for Down syndrome.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- Prenat Diagn. 2009 Dec 10;30(2):110-114.
AUTORES / AUTHORS:
- Christiansen M; Pihl K; Hedley PL; Gjerris AC; Lind PO; Larsen SO; Krebs L; Larsen T
INSTITUCIÓN / INSTITUTION:
- Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark.
RESUMEN / SUMMARY:
- BACKGROUND: ADAM12 has been shown to be an efficient maternal serum marker for Down syndrome (DS) in the first trimester; but recent studies, using a second generation assay, have not confirmed these findings. We examined the efficiency of a second generation assay for ADAM12. MATERIALS AND METHODS: ADAM12 concentrations were determined in 28 first trimester DS and 503 control pregnancies using a novel Research Delfia® ADAM12 kit. Log10MoM distributions of ADAM12 and correlations with other markers were established. Population performance of screening was estimated by Monte Carlo simulation. RESULTS: ADAM12 was significantly reduced in the first trimester in DS pregnancies with a log10MoM of -0.1621 (equivalent to 0.68 MoM) (p < 0.001). The reduction decreased with advancing gestational age. ADAM12 used with PAPP-A + hCGbeta + NT (CUB screening) increased the detection rate (DR) from 86% to 89% for a false positive rate (FPR) of 5%. When used for a fixed DR of 90%, the addition of ADAM12 resulted in a 25% reduction of the FPR. CONCLUSION: ADAM12 is a moderately effective DS marker. It is not a cost-effective addition to CUB screening, but may be used to reduce the FPR in selected high-risk cases. Copyright © 2009 John Wiley & Sons, Ltd.
TÍTULO / TITLE:
- Maternal serum human placental growth hormone at 11 to 13 weeks in trisomy 21 and trisomy 18 pregnancies.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- Prenat Diagn. 2010 Jan 25.
AUTORES / AUTHORS:
- http://dx.doi.org/10.1002/pd.2438
INSTITUCIÓN / INSTITUTION:
- Department of Obstetrics and Gynaecology, University Hospital of Heraklion, Crete, Greece.
RESUMEN / SUMMARY:
- OBJECTIVE: To investigate the maternal serum concentration of human placental growth hormone (hPGH) in trisomy 21 and trisomy 18 pregnancies at 11 to 13 weeks of gestation and to examine the possible association between fetal nuchal translucency (NT) thickness and maternal serum free beta-human chorionic gonadotrophin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A). METHODS: The maternal serum concentration of hPGH at 11 to 13 weeks was measured in a case-control study from 28 pregnancies with fetal trisomy 21, 28 with trisomy 18 and 112 pregnancies with euploid fetuses. The median hPGH multiple of the median (MoM) in trisomy 21 and trisomy 18 pregnancies were compared with euploid pregnancies. RESULTS: Serum hPGH was significantly lower in trisomy 21 (0.93 MoM) and trisomy 18 (0.62 MoM) compared to euploid pregnancies (1.02 MoM). There was a significant association between serum hPGH and PAPP-A in both the euploid (r = 0.258, p = 0.006) and trisomy 21 pregnancies (r = 0.410, p = 0.030) but not in trisomy 18 pregnancies (p = 0.445). CONCLUSION: In the first trimester, serum hPGH in trisomy 21 and trisomy 18 pregnancies is reduced. This is the opposite of findings in previous studies reporting that in the second trimester, trisomy 21 and 18 pregnancies have increased hPGH.
TÍTULO / TITLE:
- Maternal Plasma DNA Analysis with Massively Parallel Sequencing by Ligation for Noninvasive Prenatal Diagnosis of Trisomy 21.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Clin Chem. 2009 Dec 21.
AUTORES / AUTHORS:
- Chiu RW; Sun H; Akolekar R; Clouser C; Lee C; McKernan K; Zhou D; Nicolaides KH; Lo YM
INSTITUCIÓN / INSTITUTION:
- Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, and Department of Chemical Pathology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
RESUMEN / SUMMARY:
- BACKGROUND: Noninvasive prenatal diagnosis of trisomy 21 (T21) has recently been shown to be achievable by massively parallel sequencing of maternal plasma on a sequencing-by-synthesis platform. The quantification of several other human chromosomes, including chromosomes 18 and 13, has been shown to be less precise, however, with quantitative biases related to the chromosomal GC content. METHODS: Maternal plasma DNA from 10 euploid and 5 T21 pregnancies was sequenced with a sequencing-by-ligation approach. We calculated the genomic representations (GRs) of sequenced reads from each chromosome and their associated measurement CVs and compared the GRs of chromosome 21 (chr21) for the euploid and T21 pregnancies. RESULTS: We obtained a median of 12 x 10(6) unique reads (21% of the total reads) per sample. The GRs deviated from those expected for some chromosomes but in a manner different from that previously reported for the sequencing-by-synthesis approach. Measurements of the GRs for chromosomes 18 and 13 were less precise than for chr21. z Scores of the GR of chr21 were increased in the T21 pregnancies, compared with the euploid pregnancies. CONCLUSIONS: Massively parallel sequencing by ligation of maternal plasma DNA was effective in identifying T21 fetuses noninvasively. The quantitative biases observed among the GRs of certain chromosomes were more likely based on analytical factors than biological factors. Further research is needed to enhance the precision for measuring for the representations of chromosomes 18 and 13.
QUALITY OF LIFE - CALIDAD DE VIDA
TÍTULO / TITLE:
- Residential Characteristics, Social Factors, and Mortality Among Adults With Intellectual Disabilities: Transitions Out of Nursing Homes
RESUMEN / SUMMARY:
REVISTA / JOURNAL:
- INTELLECTUAL AND DEVELOPMENTAL DISABILITIES, 47 (6): 447-465 DEC 2009
AUTORES / AUTHORS:
- Hsieh, K; Heller, T; Freels, S
RESUMEN / SUMMARY:
- The present Study examined the degree to which residential characteristics and social factors are associated with mortality, after controlling for personal characteristics, among adults With intellectual disabilities who have resided in nursing homes (facilities providing skilled care and related services) at baseline in the Chicago area. Initial assessments were conducted oil 330 residents, and 2 follow ups were performed over 10 years. Seventy-one residents had died by the end of the Study. The variables examined included personal characteristics of age, gender, intellectual level, health, and adaptive behavior; residential characteristics of type of residence, size of facility, attractiveness of physical environment (cleanliness, conditions, and aesthetic appeal), and diversity of physical environment (personalization of residents` rooms and distinctiveness of all living spaces); and social factors of family involvement and community integration. The results indicated,! beyond age, adaptive behavior, and health, that size of residences, residential characteristics, and social factors are related to mortality.
TÍTULO / TITLE:
- Optimizing health care for individuals with Down syndrome in Israel.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Isr Med Assoc J. 2009 Nov;11(11):655-9.
AUTORES / AUTHORS:
- Wexler ID; Abu-Libdeh A; Kastiel Y; Nimrodi A; Kerem E; Tenenbaum A
INSTITUCIÓN / INSTITUTION:
- Department of Pediatrics, Hadassah University Medical Center, Mount Scopus Campus, Jerusalem, Israel.
RESUMEN / SUMMARY:
- BACKGROUND: Down syndrome is one of the most common chromosomal abnormalities. Children and adults with DS have significant medical problems and require life-long medical follow-up. OBJECTIVES: To determine the adequacy of medical surveillance of individuals with DS as recommended by the American Academy of Pediatrics. METHODS: The study was conducted at a multidisciplinary center specializing in the care of DS during the period 2004-2006. At their first visit to the Center, caregivers of individuals with DS were questioned about the medical status of their child including previous evaluations. Medical records brought in by the parents were reviewed. RESULTS: The caregivers of 150 individuals with DS (age ranging from newborn to 48-years-old, median age 5 years) were interviewed and the medical records were reviewed. The prevalence of specific medical problems differed between our population and the reported prevalence from other surveys. For example, 39.3% of our population had documented auditory deficits while the reported prevalence is 75%. For gastrointestinal and thyroid disease, the prevalence was higher in the studied population than that reported in the literature. In terms of compliance with the AAP recommendations, most children (94%) underwent echocardiography, but only 42.7% and 63.3% had been tested for auditory or visual acuity respectively. Only 36.3% over the age of 3 years had cervical spine films. DISCUSSION: Many individuals with DS are not receiving appropriate medical follow-up and the consequences of inadequate surveillance can be serious.
TÍTULO / TITLE:
- A father’s and physician’s perspective on Down syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- J S C Med Assoc. 2009 Oct;105(6):204-6.
AUTORES / AUTHORS:
- Duniho TL
RESUMEN / SUMMARY:
-
TÍTULO / TITLE:
- Access to genetic counseling for children with autism, Down syndrome, and intellectual disabilities.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Pediatrics. 2009 Dec;124 Suppl 4:S443-9.
AUTORES / AUTHORS:
- McGrath RJ; Laflamme DJ; Schwartz AP; Stransky M; Moeschler JB
INSTITUCIÓN / INSTITUTION:
- University of New Hampshire, Department of Health Management and Policy, Hewitt Hall, Suite 323, Durham, NH 03824, USA.
robert.mcgrath@unh.edu
RESUMEN / SUMMARY:
- OBJECTIVE: We examined the need for genetic counseling services (GCS) for families of children with autism spectrum disorder (ASD), Down syndrome (DS), and/or mental retardation (MR) and factors that influence the receipt of needed GCS for those children relative to other children with special health care needs (CSHCN). METHODS: Analysis was conducted on the 2005-2006 National Survey of Children With Special Health Care Needs, a nationally representative sample. Bivariate analyses were conducted by examining need for and receipt of GCS for children with ASD, DS, and/or MR and other CSHCN as well as differences by contextual variables using the health belief model (HBM). Logistic regression analyses were conducted to assess the relative impact of receipt of needed GCS by HBM constructs. RESULTS: Families of children with diagnoses of ASD, DS, and/or MR perceive significantly higher need for GCS than other CSHCN. The presence of a medical home is the single most important factor in facilitating access to GCS, together with the presence of insurance, particularly private or a combination of private and public insurance. As income and education attainment decrease, barriers to GCS rise. CONCLUSIONS: This analysis supports strategies for improving linkages between specialty providers and the medical home at which primary care is delivered. Increased effort should be made to attend to those who experience barriers that result from lack of insurance, poverty, low education, or racial or ethnic differences. Health professionals need to collaborate in developing solutions to underinsurance or lack of insurance for CSHCN.
TÍTULO / TITLE:
- Sexuality and persons with Down syndrome. A study from Brazil.
RESUMEN / SUMMARY:
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REVISTA / JOURNAL:
- Int J Adolesc Med Health. 2009 Jul-Sep;21(3):319-26.
AUTORES / AUTHORS:
- Bononi BM; Sant’Anna MJ; de Oliveira AC; Renattini TS; Pinto CF; Passarelli ML; Coates V; Omar HA
INSTITUCIÓN / INSTITUTION:
- Adolescent Clinical Unit, Santa Casa de Sao Paulo, Faculty of Medical Sciences, Sao Paulo, Brazil.
RESUMEN / SUMMARY:
- In recent years, important gains and changes have been observed in the life of teenagers with Down syndrome (DS) with increased inclusion into society. This review will discuss adolescence and sexuality in teenagers with DS from a descriptive study of 50 patients with DS between the ages of 10 and 20 years. The mean age was 13.5 years, 50% females; 86% went to school with 62.2% in school for over six years. Of the patients that attended school, 60% went to special education school and only 10% read and wrote correctly. In an evaluation of autonomy, 66% took showers, 78% performed their physiological needs, 77% intimate hygiene and 76% oral hygiene without help. 42% affirmed being able to do anything that is asked; 22% perform all tasks in the home; 10% felt they were incapable of doing anything and 4% used public transportation without help. 42% of the teenagers masturbated, 24% on a daily basis, 75% in private, and 25% in a public location. 42% had already kissed at a mean age of 12.9 years, mean age of the partner 16.1 years; 26.8% of these partners had DS. 82% found themselves attractive and 33% would not change anything in their appearance. We found that they presented normal development in the exercise of their sexuality, but with important difficulties in their autonomy and difficulties in school, needing careful interventions to make their social interaction the best possible. Their pubertal development was normal and they were satisfied with their body image with future perspectives of working, finding a partner, and living a normal life of getting married and having children.
TÍTULO / TITLE:
- Effects of adeno-tonsillectomy on polysomnography patterns in Down syndrome children with obstructive sleep apnea: A comparative study with children without Down syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- Int J Pediatr Otorhinolaryngol. 2010 Jan 22.
AUTORES / AUTHORS:
- Shete MM; Stocks RM; Sebelik ME; Schoumacher RA
INSTITUCIÓN / INSTITUTION:
- Otolaryngology & Head and Neck Surgery, University Tennessee Health Science Center, 910 Madison Ave, Suite 429, Memphis, TN 38163, United States.
RESUMEN / SUMMARY:
- OBJECTIVE: To determine if adeno-tonsillectomy (T&A) in children with Down syndrome (DS) improves breathing, measured by apnea hypopnea index (AHI), rapid eye movement AHI (REM-AHI) and the lowest oxygen desaturation (SaO(2)), and sleep disruption, measured by arousal index (ArI) and time spent in stages 1-4 and rapid eye movement (REM) sleep and compare these results with a group of non-DS children with obstructive sleep apnea (OSA). STUDY DESIGN: Retrospective chart review at pediatric sleep center. PATIENTS: Eleven DS and nine non-DS children underwent pre- and post-T&A polysomnography between 1997 and 2005. OUTCOME MEASURES: Pre- and post-T&A polysomnography parameters were compared using paired t-test and independent samples test. RESULTS: Mean age in DS group was 101 months and non-DS group was 80 months (64% males in DS and 88% in non-DS group). The average BMI was 29.8 and 27.6 for DS and non-DS group. The total AHI showed significant improvement after T&A but this was not as marked as the non-DS group. REM-AHI and lowest SaO(2) did not show significant change in the DS children. The non-DS group showed significant improvement in all respiratory parameters. Both groups showed mild improvement in sleep parameters. With the modest overall improvement, 27% of the DS children required no further treatment. However, 73% required CPAP, BiPAP or oxygen for persistent OSA. CONCLUSION: This study supports the fact that T&A in DS children improves some parameters of OSA, however not as markedly as in non-DS children.
TÍTULO / TITLE:
- Obstructive sleep apnea in adults with Down syndrome.
RESUMEN / SUMMARY:
-
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REVISTA / JOURNAL:
- J Clin Sleep Med. 2009 Aug 15;5(4):317-23.
AUTORES / AUTHORS:
- Trois MS; Capone GT; Lutz JA; Melendres MC; Schwartz AR; Collop NA; Marcus CL
INSTITUCIÓN / INSTITUTION:
- Department of Pediatrics and Medicine, Johns Hopkins University School of Medicine, Baltimore MD, USA.
RESUMEN / SUMMARY:
- OBJECTIVES: A high proportion of children with Down syndrome (DS) have the obstructive sleep apnea syndrome (OSAS). Although adults with DS have many predisposing factors for OSAS, this population has not been well studied. We hypothesized that OSAS is common in adults with DS, and that the severity of OSAS is worse in DS adults who are more obese. DESIGN: Cohort study. SETTING: Sleep laboratory. PARTICIPANTS: 16 adults with DS underwent evaluation for sleep disordered breathing. INTERVENTIONS: Polysomnographic results were compared to a retrospective sample of adult patients referred for clinically suspected OSAS. MEASUREMENTS AND RESULTS: Polysomnograms were abnormal in 94% of DS subjects. The median apnea hypopnea index (AHI) was 37/h (range 0-118). The median arterial oxygen saturation nadir was 75% (23% to 95%), and the median peak end-tidal CO2 was 58 (47-66) mm Hg. There was a significant correlation between body mass index and AHI (r = 0.53, p < 0.05). Sixty-three percent had an Epworth score > 10. The AHI and saturation nadir were significantly worse in DS than non-DS patients. CONCLUSIONS: Adults with DS frequently have OSAS, with obstructive apnea, hypoxemia, hypoventilation, and sleep fragmentation. The severity of OSAS correlated with obesity. We speculate that the complications of untreated OSAS (cardiovascular disease, increased mortality, and neurobehavioral morbidities including daytime sleepiness and impaired cognitive function) commonly overlap with the manifestations of DS and therefore may not elicit a prompt investigation in these patients. We speculate that OSAS is an important, but potentially treatable, cause of morbidity in adults with DS.
TÍTULO / TITLE:
- Management of foreign body in esophagus with rigid bronchoscopy.
RESUMEN / SUMMARY:
-
Enlace al Resumen
REVISTA / JOURNAL:
- Am J Emerg Med. 2010 Jan;28(1):116.e5-6.
AUTORES / AUTHORS:
- Delgado-Plasencia L; Manes-Bonet N; Torres Monzon E
INSTITUCIÓN / INSTITUTION:
- Department of General Surgery, University Hospital of the Canary Islands, 38320-La Laguna Islas Canarias, España
lucianodelgado1@gmail.com
RESUMEN / SUMMARY:
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