Atrial Fibrillation as an Uncommon Presentation for RASopathy in an Adult
Document Type
Article
Abstract
Background
RASopathies are genetic diseases caused primarily by mutations in RAS/MAPK pathway genes. Cardiac manifestations are common and include congenital defects, valvular abnormalities and hypertrophic cardiomyopathy (HCM). Atrial tachyarrhythmias may rarely occur but are not commonly initial presenting features.
Case
A 29-year-old Caucasian man with subtle, previously unrecognized, craniofacial dysmorphic features was referred to HCM Clinic. He did not manifest developmental delays, skin lesions, history of malignancy, or short stature. Patient had recurrent episodes of atrial fibrillation with rapid ventricular response for 6 years and was managed with rate and rhythm control medications. Recurrent episodes required electrical cardioversion and later ablation with pulmonary vein isolation. During all these episodes electrolytes, kidney function and complete blood counts were within normal limits. Transthoracic echocardiogram had shown severe unexplained left ventricular hypertrophy with features suggesting non-obstructive HCM (asymmetric basal septal wall hypertrophy, 16 mm) with vigorous left ventricular systolic function. Cardiac magnetic resonance imaging confirmed left ventricular hypertrophy (basal septal thickness ~16 mm) without significant valvular pathology or myocardial fibrosis. Notable family history included father with history of ventricular tachycardia, ICD implantation and appropriate shocks, and paternal uncle with sudden death.
Decision-making
Patient underwent genetic testing (100 gene arrhythmia and cardiomyopathy panel) to assess for pathogenic mutations associated with sarcomeric HCM or its phenocopies, which revealed a pathogenic variant in the RIT1 gene (exon 5, c.251C>T, p. ALA84Val), one of known mutations associated with autosomal dominant RASopathy spectrum disorders. The patient was referred to the National Cancer Institute to participate in the RASopathy natural history study.
Conclusion
We present an adult with HCM phenotype and a pathogenic mutation in RIT1 gene unusually presenting with recurrent and refractory atrial fibrillation. Management of HCM in such setting remains inadequately described.
First Page
2533
DOI
10.1016/S0735-1097(23)02977-7
Publication Date
3-7-2023
Recommended Citation
Gasimli-Gamache L, Shirani J. ATRIAL FIBRILLATION AS AN UNCOMMON PRESENTATION FOR RASOPATHY IN AN ADULT. Journal of the American College of Cardiology. 2023 Mar 7;81(8_Supplement):2533-.