Böttcher Ana Kalise, Siqueira Monique Banik, Malgarezi Natasha, Nunes Marcela Rodrigues, Mergener Rafaella, Kalil Luisa Pigatto, Trevisan Patrícia, Zen Paulo Ricardo Gazzola
Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil.
Universidade do Vale do Rio dos Sinos, São Leopoldo, RS, Brazil.
Rev Paul Pediatr. 2025 Jan 20;43:e2024133. doi: 10.1590/1984-0462/2025/43/2024133. eCollection 2025.
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.
3p缺失综合征是一种罕见的单体疾病，涉及整个3号染色体短臂的缺失。其缺失常发生在远端区域（3p25 - pter），但断点存在变异且临床表现复杂，先天性心脏缺陷较为罕见。我们报告首例与3p - 综合征相关的左心发育不全综合征及轻微畸形特征病例。此外，我们旨在建立基因 - 表型关联。
通过核型分析做出诊断，随后对与3p - 综合征中先天性心脏缺陷或左心发育不全综合征相关的可能候选基因进行文献调查和计算机生物信息学分析。所有分析的可能影响心脏形成的基因都位于3p25.3区域，与我们病例中新生儿的缺失区域（3p26）相邻。考虑到核型分析的技术局限性以及每个评估基因的证据强度和基因座接近度，CAV3基因可能发生了未被识别的部分断裂。
我们发现基因CAV3与左心发育不全综合征之间存在间接关系，因为它与心肌病和孤立性心脏缺陷密切相关。此外，我们病例的细胞遗传学带为界定3p综合征关键心脏区域提供了新信息，自1986年以来这一讨论一直在进行。因此，我们强调对心脏发育不全和畸形患者进行细胞遗传学检查的重要性，有助于诊断、预后定义以及为家庭提供遗传咨询。
