Related Experiment Videos
Penetrance of familial hypertrophic cardiomyopathy
Insights
Familial hypertrophic cardiomyopathy (FHC) penetrance is incomplete at 69% and increases with age, reaching 95% in individuals over 50. Penetrance is also higher in males compared to females.
Area of Science:
- Cardiology
- Genetics
- Medical Research
Background:
- Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant cardiac condition.
- The penetrance of FHC has been a subject of ongoing debate.
- Previous assessments of FHC penetrance have not utilized large, genotyped populations.
Purpose of the Study:
- To re-evaluate the penetrance of FHC in a large, genotyped cohort.
- To assess FHC penetrance based on age and sex.
- To analyze penetrance across different mutations within families.
Main Methods:
- Studied 178 individuals from ten families with known FHC mutations.
- Genetically identified 90 affected individuals carrying 9 different mutations in 3 genes.
- Assessed penetrance using echocardiographic and electrocardiographic criteria.
Main Results:
- Overall FHC penetrance was found to be incomplete at 69%.
- Penetrance demonstrated a clear age-related pattern: 55% (10-29 years), 75% (30-49 years), and 95% (over 50 years).
- Penetrance was significantly higher in males (77%) compared to females (58%), with an odds ratio of 3.98.
Conclusions:
- FHC penetrance is incomplete and significantly influenced by age and sex.
- These findings have crucial implications for genetic counseling regarding FHC.
- The results also provide valuable insights for future genetic linkage analyses in FHC.
Abstract:
Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant cardiac disease for which the penetrance remains a much-debated issue. Since the recent identification of the genes involved in the disease, the penetrance of FHC has not been reassessed in a large genotyped population. The aim of our study was therefore to evaluate it, according to age and sex, in ten families with previously identified mutations. Among 178 individuals we studied, 90 were genetically affected (9 different mutations in 3 genes). We found that penetrance, assessed by classical echocardiographic and electrocardiographic criteria, was (1) incomplete: 69%; (2) age-related: 55% between 10 and 29 years old, 75% between 30 and 49 y. and 95% over 50 y.; (3) greater in males than in females: 77% vs 58%, age-adjusted odds ratio: 3.98, CI 95%: 1.34 to 11,48; (4) similar for the genes analyzed. The consequences of these results for genetic counseling and linkage analyses are discussed.