3p deletion syndrome is a rare monosomal disease that encompasses deletions throughout the short arm of chromosome 3. It is often in the distal region (3p25-pter), but variations in breakpoints and a complex clinical manifestation exist, with congenital heart defects being considered rare. We present the first case of hypoplastic left heart syndrome and minor dysmorphic features associated with 3p- syndrome. Furthermore, we aim to establish a gene-phenotype association. The diagnosis was made by karyotyping, followed by a literature investigation and in silico bioinformatic analysis about the possible candidate genes associated with congenital heart defects or hypoplastic left heart syndrome in 3p- syndrome. All genes analyzed that could affect heart formation are located in the 3p25.3 region, adjacent to the deleted region in the newborn from our case (3p26). Taking into account the technical limitations of the karyotype and the strength of evidence from each gene evaluated and locus proximity, it is likely that an unidentified partial break in the CAV3 gene occurred. We identified an indirect relation between gene CAV3 and hypoplastic left heart syndrome due to its strong association with cardiomyopathies and isolated cardiac defects. Furthermore, the cytogenetic band from our case is new information for the delimitation of a critical cardiac region on 3p syndrome, a discussion that has been ongoing since 1986. Thus, we reinforce the importance of cytogenetic investigation in patients with hypoplastic hearts and dysmorphia, assisting in diagnosis, definition of prognosis, and genetic counseling for the family. A síndrome da deleção 3p é uma doença monossômica rara que engloba deleções em todo o braço curto do cromossomo 3. Frequentemente está na região distal (3p25-pter), mas apresenta variações nos pontos de quebra e uma manifestação clínica complexa, cujas cardiopatias congênitas são consideradas raras. Apresentamos aqui o primeiro caso de síndrome do coração esquerdo hipoplásico e características dismórficas menores na síndrome 3p-. Além disso, buscamos estabelecer uma associação gene-fenótipo. O diagnóstico foi feito por cariótipo e procedeu-se a uma investigação bibliográfica e análise bioinformática in silico sobre os possíveis genes associados a cardiopatias congênitas ou síndrome do coração esquerdo hipoplásico na síndrome da deleção 3p. Todos os genes analisados que poderiam afetar a formação do coração estão localizados na região 3p25.3, adjacente à região deletada no recém-nascido do nosso caso (3p26). Tendo em conta as limitações técnicas do cariótipo, a força da evidência de cada gene avaliado e a proximidade do locus, é provável que tenha ocorrido uma quebra parcial não identificada no gene CAV3. Identificamos uma relação indireta entre o gene CAV3 e a síndrome do coração hipoplásico esquerdo, em razão da sua forte associação com cardiomiopatias e defeitos cardíacos isolados. Além disso, a banda citogenética do nosso caso é uma informação nova para a delimitação de uma região cardíaca crítica na síndrome 3p, discussão que está em andamento desde 1986. Assim, reforçamos a importância da investigação citogenética em pacientes com coração hipoplásico e dismorfias auxiliando no diagnóstico, definição de prognóstico e aconselhamento genético para a família.

While Miller-Dieker syndrome critical region deletions are well known delineated anomalies, submicroscopic duplications in this region have recently emerged as a new distinctive syndrome. So far, only few cases have been described overlapping 17p13.3 duplications. In this study, we report on clinical and cytogenetic characterization of two new cases involving 17p13.3 and 3p26 chromosomal regions in two sisters with familial history of lissencephaly. Fluorescent In Situ Hybridization and array Comparative Genomic Hybridization were performed. A deletion including the critical region of the Miller-Dieker syndrome of at least 2,9 Mb and a duplication of at least 3,6 Mb on the short arm of chromosome 3 were highlighted in one case. The opposite rearrangements, 17p13.3 duplication and 3p deletion, were observed in the second case. This double chromosomal aberration is the result of an adjacent 1:1 meiotic segregation of a maternal reciprocal translocation t(3,17)(p26.2;p13.3). 17p13.3 and 3p26 deletions have a clear range of phenotypic features while duplications still have an uncertain clinical significance. However, we could suggest that regardless of the type of the rearrangement, the gene dosage and interactions of CNTN4, CNTN6 and CHL1 in the 3p26 and PAFAH1B1, YWHAE in 17p13.3 could result in different clinical spectrums.

Neural tube defects belong to the second most common group of congenital anomalies, after heart defects, which can be diagnosed by prenatal ultrasonography. Rarely, neural tube defects can be associated with chromosomal abnormalities, including full and partial aneuploidies. We report a familial fetal case with syndromic spina bifida and discuss its association with partial 3q duplication and partial 5p deletion. Clinical findings of three affected family members in two generations and two carriers of the balanced translocation are described. Conventional cytogenetic and fluorescence in situ hybridization (FISH) analysis of the carrier, as well as subtelomeric multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (CGH) analysis on the DNA extracted from affected family members was performed. Subtelomeric FISH analysis of the proposita revealed balanced reciprocal translocation between the long arm of chromosome 3 and short arm of chromosome 5. Subtelomeric MLPA screening of the first child revealed the deletion in 5p15.33 and duplication in 3q29 chromosomal loci, the finding consisting of the unbalanced rearrangement involving the short arm of chromosome 5 and long arm of chromosome 3. Array CGH analysis of the DNA of the second affected child revealed a 31.1Mb duplication of 3q26.1-qter and a 33.6Mb deletion of 5p13.33-pter. Our report serves to emphasize the consistency in the prenatal sonographic feature of spina bifida in consecutive pregnancies with fetuses associated with partial trisomy 3q (3q26.1-qter) and partial monosomy 5p (5p13.33-pter). The use of molecular cytogenetic technologies such as array CGH and FISH is important for clarifying any type of unbalanced chromosome rearrangement.