Division of Medical Genetics, Stanford University, Stanford, California, USA.
Division of Human Genetics and Molecular Biology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Am J Med Genet A. 2021 May;185(5):1486-1493. doi: 10.1002/ajmg.a.62146. Epub 2021 Mar 8.
The RASopathies are a group of similar genetic syndromes with cardiovascular abnormalities, characteristic facial features, short stature, abnormalities of the skin and musculoskeletal system, and variable neurodevelopmental challenges. The most common cardiovascular abnormalities include pulmonary valvular stenosis and hypertrophic cardiomyopathy. Congenital polyvalvular disease (CPVD) refers to congenital dysplasia of two or more cardiac valves. We diagnosed a RASopathy in two individuals with CPVD and noted that CPVD in RASopathies has rarely been reported in the literature. Thus, we performed a retrospective chart review and literature review to investigate the association and characterize the phenotype of CPVD in the RASopathies. CPVD was present in 2.5% (n = 6/243) of individuals in our RASopathy cohort. Involvement of two cardiac valves, commonly the aortic and pulmonic valves, was seen in the majority of individuals (6/8; 75%) in our cohort, but only 27% (3/11) of reported CPVD and RASopathy cases in the literature. CPVD should be considered an associated cardiovascular phenotype of the RASopathies, which has implications for diagnosis and management.
RAS 相关疾病是一组具有心血管异常、特征性面部特征、身材矮小、皮肤和肌肉骨骼系统异常以及不同程度神经发育挑战的相似遗传综合征。最常见的心血管异常包括肺动脉瓣狭窄和肥厚型心肌病。先天性多瓣膜病 (CPVD) 是指两个或多个心脏瓣膜的先天性发育不良。我们在两名 CPVD 患者中诊断出一种 RAS 相关疾病，并注意到 CPVD 在 RAS 相关疾病中很少在文献中报道。因此，我们进行了回顾性图表审查和文献复习，以研究 CPVD 在 RAS 相关疾病中的关联和表型特征。CPVD 存在于我们的 RAS 相关疾病队列中的 2.5%（n=6/243）个体中。在我们的队列中，大多数个体（6/8；75%）存在两个心脏瓣膜的受累，通常是主动脉瓣和肺动脉瓣，但在文献中仅报告了 27%（3/11）的 CPVD 和 RAS 相关疾病病例。CPVD 应被视为 RAS 相关疾病的一种相关心血管表型，这对诊断和管理具有重要意义。
