Hypertrophic Cardiomyopathy

Abstract

MD; for the EUROGENE Heart Failure ProjectBackground-Hypertrophic cardiomyopathy is an autosomal-dominant disorder in which 10 genes and numerous mutations have been reported. The aim of the present study was to perform a systematic screening of these genes in a large population, to evaluate the distribution of the disease genes, and to determine the best molecular strategy in clinical practice. Methods and Results-The entire coding sequences of 9 genes (MYH7, MYBPC3, TNNI3, TNNT2, MYL2, MYL3, TPM1, ACTC, and TNNC1) were analyzed in 197 unrelated index cases with familial or sporadic hypertrophic cardiomyopathy. Disease-causing mutations were identified in 124 index patients (Ϸ63%), and 97 different mutations, including 60 novel ones, were identified. The cardiac myosin-binding protein C (MYBPC3) and ␤-myosin heavy chain (MYH7) genes accounted for 82% of families with identified mutations (42% and 40%, respectively). Distribution of the genes varied according to the prognosis (Pϭ0.036). Moreover, a mutation was found in 15 of 25 index cases with "sporadic" hypertrophic cardiomyopathy (60%). Finally, 6 families had patients with more than one mutation, and phenotype analyses suggested a gene dose effect in these compound-heterozygous, double-heterozygous, or homozygous patients. Conclusion-These results might have implications for genetic diagnosis strategy and, subsequently, for genetic counseling. First, on the basis of this experience, the screening of already known mutations is not helpful. The analysis should start by testing MYBPC3 and MYH7 and then focus on TNNI3, TNNT2, and MYL2. Second, in particularly severe phenotypes, several mutations should be searched. Finally, sporadic cases can be successfully screened. (Circulation.

Inverted U-Shaped Relation Between the Risk of Sudden Cardiac Death and Maximal Left Ventricular Wall Thickness in Hypertrophic Cardiomyopathy

“…27 In addition, none of the observed mutations have been consistently linked with MWT ≥35 mm. Complex genotypes have been associated with severe hypertrophy, [28][29][30] but this study shows that the reverse is not true because the majority of cases of MWT ≥35 mm were not linked to a complex genotype. HCM with extreme MWT can be a feature of some glycogen storage diseases and it is conceivable that some patients had undiagnosed metabolic disorders.…”

Alcohol septal ablation in hypertrophic cardiomyopathy utilizing a longitudinal 17-year study (mean 10.8). Observation follow-ups taken at a single medical centre

“…It occurs in approximately 1 per 500 people, and in about 50% of these family burden can be established [1,2]. While the non-obstructive form often does not cause a significant impairment in exercise capacity (sometimes it even does not impede practising sport), the obstruction of the outflow from the LV can lead to severe clinical symptoms [6].…”

“…It occurs in approximately 0.2% of the population; approximately 50% can be attributed to family burden [1,2]. The prognosis is relatively good for most patients; in mild forms, the risk of severe cardiac complications (sudden death, dangerous arrhythmias) is slightly higher than in the healthy population.…”

Genetic determinants of heart failure: facts and numbers

“…It is the most common hereditary cardiac disease with a prevalence of 1:500 25. HCM is a frequent cause of sudden cardiac death in young and asymptomatic individuals.…”