Dominant inheritance and intra-familial variations in the association of Sturge-Weber and Klippel-Trenaunay-Weber syndromes

This case report shows a genealogical study where a woman has limb hypertrophy and her son has an association of Sturge-Weber syndrome with Klippel-Trenaunay-Weber syndrome. The Sturge-Weber and Klippel-Trenaunay-Weber syndromes appear to be different manifestations of the same affliction. Familial aggregation exists and transmission may be almost imperceptible between generations. Identification of minor manifestations may prove to be a valuable contribution to genetic counseling of families and the prevention of new cases

O contexto diagnóstico de indivíduos com autismo leve

Introdução:A Síndrome de Asperger (AS)é um distúrbio do neuro desenvolvimento;  parte do diagnóstico definido como Transtorno do Espectro Autista (TEA), também considerado como autismo leve, segundo a nova classificação do Manual Estatístico e Diagnóstico de Doenças Mentais (DSM-5). Indivíduos com AS apresentam déficits sociais e comportamentos estereotipados. Objetivo: Investigar o contexto e trajetória do diagnóstico de AS, desde a idade de percepção dos sintomas, idade da primeira avaliação clínica, a hipótese diagnóstica que precedeu o diagnóstico conclusivo, período de tempo entre a percepção dos sintomas e o diagnóstico conclusivo, a especialidade do profissional que diagnosticou e as principais recomendações recebidas no diagnóstico. Casuística e Métodos: Quarenta e quatro indivíduos; 38 homens e seis mulheres foram investigados por meio de avaliação clínica e entrevista semiestruturada. Resultados: A idade da percepção de que havia algo de diferente variou de um a nove anos (média=3.2 anos), e os primeiros a percebê-lo foram os pais (57%), e os últimos foram os profissionais da saúde (7%). A primeira avaliação diagnóstica foi realizada entre um e 15 anos de idade. O diagnóstico inicial mais comum foi de Transtorno de Déficit de Atenção e Hiperatividade (34,1%) realizado na maioria parte pelo neurologista (54,5%). O tempo médio entre a percepção de que havia algo de diferente no desenvolvimento da criança e o diagnóstico de SA foi de 7,8 anos, realizado por psiquiatras na maioria dos casos (61,3%).  As principais recomendações foram frequentar escola regular (68,1%), realizar psicoterapia (59%), usar medicação (56,8%), realizar Fonoterapia (38,6%) e avaliação genética (36,3%). Conclusão: Os resultados mostram que o contexto do diagnóstico de AS faz-se tardio; mesmo do fenótipo comportamental considerado mais brando é complexo. A maioria dos profissionais da saúde não está preparada o suficiente para detecção precoce de SA, o que também compromete a intervenção imediata, isto é, essencial   nestes casos

Down Syndrome Resulting from a Rare non-Robertsonian Translocation t(11;21)(p13;q22)

Introduction: Down syndrome (DS) is a common genetic disorder, occurring in approximately 1 in 700 births. It results from an extra copy (triplication) of the whole or part of the long arm of chromosome 21 caused by different cytogenetic alterations: free trisomy, Robertsonian translocations, mosaicism, duplication of the critical region and other structural rearrangements. Non-Robertsonian chromosome translocations are very rare events with few cases reported. Case Report: We identified the non-Robertsonian translocation t(11;21)(p13;q22) and two chromosomes 21 in a female child referred with a clinical diagnosis of trisomy 21.  The infant developed the transient myeloproliferative disorder at 17 months. Cytogenetic analysis was performed in lymphocytes and bone marrow metaphases according to standard procedure - G banding and fluorescence in situ hybridization.  The karyotype study of the parents revealed that her phenotypically normal mother carries the same reciprocal translocation. Conclusion: This is the second report of the translocation t(11;21)(p13;q22),  the first one resulting in DS.  This description expands knowledge about cytogenetic variability in the etiology of DS. Future studies are needed to investigate the long-term clinical effects of the trisomy 21 associated with t(11;21)(p13;q22)

Investigation of 15q11-q13, 16p11.2 and 22q13 CNVs in Autism Spectrum Disorder Brazilian Individuals with and without Epilepsy

Copy number variations (CNVs) are an important cause of ASD and those located at 15q11-q13, 16p11.2 and 22q13 have been reported as the most frequent. These CNVs exhibit variable clinical expressivity and those at 15q11-q13 and 16p11.2 also show incomplete penetrance. In the present work, through multiplex ligation-dependent probe amplification (MLPA) analysis of 531 ethnically admixed ASD-affected Brazilian individuals, we found that the combined prevalence of the 15q11-q13, 16p11.2 and 22q13 CNVs is 2.1% (11/531). Parental origin could be determined in 8 of the affected individuals, and revealed that 4 of the CNVs represent de novo events. Based on CNV prediction analysis from genome-wide SNP arrays, the size of those CNVs ranged from 206 kb to 2.27 Mb and those at 15q11-q13 were limited to the 15q13.3 region. In addition, this analysis also revealed 6 additional CNVs in 5 out of 11 affected individuals. Finally, we observed that the combined prevalence of CNVs at 15q13.3 and 22q13 in ASD-affected individuals with epilepsy (6.4%) was higher than that in ASD-affected individuals without epilepsy (1.3%; p<0.014). Therefore, our data show that the prevalence of CNVs at 15q13.3, 16p11.2 and 22q13 in Brazilian ASD-affected individuals is comparable to that estimated for ASD-affected individuals of pure or predominant European ancestry. Also, it suggests that the likelihood of a greater number of positive MLPA results might be found for the 15q13.3 and 22q13 regions by prioritizing ASD-affected individuals with epilepsy.Support was provided by FAPESP-INCT - grant number: 2008/57899-7; FAPESP-CEPID - grant number: 2013/08028-1; CNPq [http://www.fapesp.br/]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Birth defects in newborns and stillborns: an example of the Brazilian reality

<p>Abstract</p> <p>Background</p> <p>This study constitutes a clinical and genetic study of all newborn and stillborn infants with birth defects seen in a period of one year in a medical school hospital located in Brazil. The aims of this study were to estimate the incidence, causes and consequences of the defects.</p> <p>Methods</p> <p>For all infants we carried out physical assessment, photographic records, analysis of medical records and collection of additional information with the family, besides the karyotypic analysis or molecular tests in indicated cases.</p> <p>Result</p> <p>The incidence of birth defects was 2.8%. Among them, the etiology was identified in 73.6% (ci95%: 64.4-81.6%). Etiology involving the participation of genetic factors single or associated with environmental factors) was more frequent 94.5%, ci95%: 88.5-98.0%) than those caused exclusively by environmental factors (alcohol in and gestational diabetes mellitus). The conclusive or presumed diagnosis was possible in 85% of the cases. Among them, the isolated congenital heart disease (9.5%) and Down syndrome (9.5%) were the most common, followed by gastroschisis (8.4%), neural tube defects (7.4%) and clubfoot (5.3%). Maternal age, parental consanguinity, exposure to teratogenic agents and family susceptibility were some of the identified risk factors. The most common observed consequences were prolonged hospital stays and death.</p> <p>Conclusions</p> <p>The current incidence of birth defects among newborns and stillbirths of in our population is similar to those obtained by other studies performed in Brazil and in other underdeveloped countries. Birth defects are one of the major causes leading to lost years of potential life. The study of birth defects in underdeveloped countries should continue. The identification of incidence, risk factors and consequences are essential for planning preventive measures and effective treatments.</p

Dominant inheritance and intra-familial variations in the association of Sturge-Weber and Klippel-Trenaunay-Weber syndromes

This case report shows a genealogical study where a woman has limb hypertrophy and her son has an association of Sturge-Weber syndrome with Klippel-Trenaunay-Weber syndrome. The Sturge-Weber and Klippel-Trenaunay-Weber syndromes appear to be different manifestations of the same affliction. Familial aggregation exists and transmission may be almost imperceptible between generations. Identification of minor manifestations may prove to be a valuable contribution to genetic counseling of families and the prevention of new cases