RESUMEN
Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lateral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female patients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplification (MLPA) was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genes SHH, ZIC2, SIX3 and TGIF were performed in 119 patients, revealing eight mutations in SHH, two mutations in SIX3 and two mutations in ZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correlations and contribute to the development of additional strategies for the analysis of new cases.
RESUMEN
Fundamentos: Diferentes índices de incidência das cardiopatias congênitas são descritos na literatura dependendo da idade da população analisada e dos tipos de malformações incluídas. No Brasil, notadamente nas regiões norte e nordeste, não existem dados sobre a real incidência de cardiopatias congênitas. Objetivo: Descrever o perfil das cardiopatias congênitas (CC) num serviço público de referência do estado da Paraíba, Brasil. Métodos: Estudo descritivo e retrospectivo baseado em dados institucionais referentes ao Estudo Colaborativo Latino-Americano de Malformações Congênitas (ECLAMC), coletados entre janeiro 2001 e dezembro 2011. As variáveis estudadas foram: peso ao nascer, idade gestacional, sexo, município de origem, tipo de cardiopatia, faixa etária e escolaridade dos pais, história de malformações na família, consanguinidade e antecedentes familiares. Resultados: Dos 70 857 nascimentos consecutivos analisados, o diagnóstico de CC foi relatado em 290, e o tipo do defeito foi determinado em 232. Destas, 37,8 % eram cardiopatias de shunt esquerdo-direito, 9,1 % obstrutivas acianogênicas, 5,6 % obstrutivas cianogênicas e 10,3 % cardiopatias complexas. A cardiopatia foi achado isolado em 81,0 % dos casos. Conclusão: A incidência de CC nesta série foi inferior àquela relatada na literatura. Isto provavelmente reflete a dificuldade para a realização do diagnóstico precoce.
Background: Different congenital heart disease rates are described in the literature, depending on the age of the population studied and the types of malformations included. In Brazil, especially in the North and Northeast, there are no data on actual congenital heart disease rates. Objective: To describe the profile of congenital heart diseases (CHD) observed in a government-run reference facility in Paraíba State, Northeast Brazil. Methods: A descriptive retrospective study based on institutional data drawn from the Collaborative Latin American Study of Congenital Malformations (ECLAMC) compiled between January 2001 and December 2011. The variables analyzed were: birthweight, gestational age, gender, birthplace (municipality), type of congenital heart defect, age and education levels of parents, family history of congenital defects, consanguinity and family precedents. Results: Through an analysis of 70,857 consecutive births, 290 diagnoses of CHD were reported, with defect types established for 232 of them: 37.8% left-to-right shunt lesions, 9.1% acyanotic obstructive lesions, 5.6% cyanotic obstructive and 10.3% complex congenital heart diseases. Heart defects were an isolated finding in 81% of cases. Conclusion: The CHD rate in this series was below that reported in the literature, probably reflecting difficulties is establishing early diagnoses.