RAF1 mutation leading to hypertrophic cardiomyopathy in a Chinese family with a history of sudden cardiac death: A diagnostic insight into Noonan syndrome

Background: Hypertrophic cardiomyopathy (HCM) is predominantly caused by mutations in sarcomeric genes. However, a subset of cases is attributed to genetic disorders unrelated to sarcomeric genes, such as Noonan syndrome (NS) and other RASopathies. In this study, we present a family with a history of sudden cardiac death (SCD) and focus on two adults with syndromic left ventricular hypertrophy (LVH).

Methods: Clinical evaluations, including echocardiography, were conducted to assess cardiac manifestations. Whole-exome sequencing was performed to identify potential genetic variants underlying syndromic LVH in the study participants.

Results: Whole-exome sequencing revealed a missense variant in the RAF1 gene, c.782C>T (p.Pro261Leu). This variant confirmed the diagnosis of NS in the affected individuals.

Conclusion: The findings of this study underscore the importance of family history investigation and genetic testing in diagnosing syndromic LVH. By identifying the underlying genetic cause, clinicians can better understand the etiology of RAS-HCM and its association with SCD in young adults.