Compound MYH7 Mutations

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetically heterogeneous disease associated with sudden cardiac death (SCD). Risk stratification is challenging in genotype-positive individuals with borderline phenotypic expression. CASE SUMMARY: A 54-year-old man was referred for SCD risk stratification in familial HCM. His daughter had obstructive HCM, underwent septal myomectomy, and received an implantable cardioverter-defibrillator after a cardiac arrest. The patient was asymptomatic with mild septal hypertrophy and nonsustained ventricular tachycardia. Genetic testing revealed 2 pathogenic MYH7 variants in his daughter (Ala655Thr and Gly571Arg); the patient carried only Ala655Thr, whereas his wife carried Gly571Arg. Repeat cardiac magnetic resonance imaging (MRI) under anesthesia revealed late gadolinium enhancement burden of 23%, prompting implantable cardioverter-defibrillator insertion. DISCUSSION: This case underscores the value of cardiac MRI and genetic testing in individualizing SCD risk assessment when conventional HCM markers are insufficient. TAKE-HOME MESSAGES: Genotype-phenotype discordance in familial HCM underscores the need for family-based genetic evaluation and individualized risk stratification. Cardiac MRI is invaluable for SCD risk assessment in ambiguous cases.