Authors: Mehdi Guedira , Hind Hibatouallah , Jaouad Nguadi , Hicham Bouzelmat , Aatif Benyass

Abstract

Background: Hypertrophic cardiomyopathy (HCM) due to sarcomeric variants shows age-dependent penetrance and wide intrafamilial variability. The MYH7 p.Arg719Gln variant has been labelled “malignant,” a label current guidelines no longer support because genotype is excluded from validated sudden cardiac death (SCD) risk models.

Case Presentation: A four-generation Moroccan family was referred after five premature sudden deaths in young relatives. The pathogenic MYH7 c.2156G>A (p.Arg719Gln) variant, first identified in the proband, was found in seven relatives (five female). Only the three adults (all women) met diagnostic criteria for HCM (non-obstructive hypertrophy, maximal septal thickness 15.5–17 mm). The four younger carriers did not: two children had sub-diagnostic septal z-scores (≈1.5 and ≈1.0) and two had no hypertrophy, yet the youngest showed markedly increased ECG voltage out of proportion to wall thickness. Non-carriers were released from surveillance.

Conclusion: This family shows both the yield and the limits of cascade testing. Because none of the deceased was genotyped, the variant cannot be assumed to have caused the deaths; management, including defibrillator decisions, must rest on validated, age-specific risk assessment rather than on genotype

Keywords: Cardiomyopathy, hypertrophic, MYH7 protein, human, death, sudden, cardiac, genetic testing, pedigree; ohenotype.