Congenital polyvalvular disease expands the cardiac phenotype of the RASopathies

• Published in: American journal of medical genetics. Part A Vol. 185; no. 5; pp. 1486 - 1493
• Main Authors: Matalon, Dena R., Stevenson, David A., Bhoj, Elizabeth J., Santani, Avni B., Keena, Beth, Cohen, Meryl S., Lin, Angela E., Sheppard, Sarah E., Zackai, Elaine H.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-05-2021; Wiley Subscription Services, Inc
• Subjects: Adolescent; Aorta; Aortic Valve - pathology; cardiofaciocutaneous (CFC) syndrome; Cardiomyopathy; Cardiomyopathy, Hypertrophic - epidemiology; Cardiomyopathy, Hypertrophic - genetics; Cardiomyopathy, Hypertrophic - pathology; Cardiovascular Abnormalities - epidemiology; Cardiovascular Abnormalities - genetics; Cardiovascular Abnormalities - pathology; Child; Child, Preschool; Congenital diseases; connective tissue disease; Coronary artery disease; Dwarfism - genetics; Dwarfism - pathology; Dysplasia; Facies; Female; Genotype & phenotype; Heart Defects, Congenital - genetics; Heart Defects, Congenital - pathology; Heart diseases; Humans; Infant; Infant, Newborn; Literature reviews; Male; Musculoskeletal Abnormalities - epidemiology; Musculoskeletal Abnormalities - genetics; Musculoskeletal Abnormalities - pathology; Musculoskeletal system; Noonan Syndrome; Phenotype; Phenotypes; polyvalvular disease; Protein Tyrosine Phosphatase, Non-Receptor Type 11 - genetics; Proto-Oncogene Proteins B-raf - genetics; PTPN11; Pulmonary Valve Stenosis - epidemiology; Pulmonary Valve Stenosis - genetics; Pulmonary Valve Stenosis - pathology; ras Proteins - genetics; RASopathies; Skin Abnormalities - genetics; Skin Abnormalities - pathology; Stenosis; cardiofaciocutaneous (CFC) syndrome; polyvalvular disease; PTPN11; RASopathies; Noonan syndrome; connective tissue disease
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.62146

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.