New malignant mutation in hypertrophic cardiomyopathy

Abstract A 62–year–old man diagnosed with non–obstructive hypertrophic cardiomyopathy and dual–chamber pacemaker wearer since the age of 40, for third–degree atrioventricular block, came to our attention for atrial fibrillation (AF) episodes (one complicated by cardiogenic shock and multiorgan failure) and flutter with high ventricular response. For a progressive worsening of the systolic function, and the onset of multiple episodes of sustained ventricular tachycardia, an upgrade to the defibrillator was performed, which, in the following months, intervened appropriately for recurrences of ventricular arrhythmias. The patient was admitted to our ward for exacerbation of heart failure. The echocardiography showed moderate concentric hypertrophy with mild ventricular dilatation and ejection fraction 33%, inferior and inferoseptal wall, and apex akinesia with thrombotic apposition. Due to a sudden deterioration of the clinical conditions, the patient died. After genetic counseling the patient‘s family agreed to genetic testing in the proband. This highlighted the presence of a missense mutation, i.e. the substitution of the cysteine ​​residue with a serine, in the codon 905 of the MYH7 gene, encoding the cardiac isoform of myosin heavy chain. The mutation is probably pathogenetic as it falls in the region where most of the missense variants are clustered and statistically associated with the HCM phenotype. Only in one previous case of HCM was detected a mutation of the same codon, Cys905Phe. Several studies have reported that AF tends to be more prevalent in patients carrying MYH7 mutations and is associated with a substantial risk of heart failure–related mortality, stroke, and severe functional disability. Knowledge of the entire spectrum of MYH7 mutations, especially those related to a high arrhythmic burden or SCD, combined with an accurate clinical and molecular characterization of the patient, can improve the genotype–phenotype correlation by clarifying the mechanism of HCM and allowing a better clinical and therapeutic decision–making of patients.