Heart failure & cardiomyopathiesMeta-analysis
Meta-Analysis of Penetrance and Systematic Review on Transition to Disease in Genetic Hypertrophic Cardiomyopathy
- Systematic review and meta-analysis
- random-effects generalized linear mixed model
Authors' conclusion
The penetrance of P/LP variants is highly variable and influenced by currently undefined and context-dependent genetic and environmental factors.
Study context
- Population
- Carriers of P/LP variants in sarcomere or sarcomere-related genes (genetic hypertrophic cardiomyopathy)455 full-text manuscripts assessed
- Comparison
- Clinically-based studies vs population or community-based studies
- Outcome
- Penetrance (proportion of P/LP variant carriers who develop HCM)
Pooled result
As reported in the abstract
Family/clinical studies: penetrance across all genes in nonproband relatives carrying P/LP variants identified during cascade screening
57% (95% CI, 52%-63%)
Population-based studies: penetrance of hypertrophic cardiomyopathy (HCM) in incidentally identified P/LP variant carriers
≈11% (0% in Atherosclerosis Risk in Communities to 18% in UK Biobank)
Further pooled results
Prevalence of sarcomere variants
- Family/clinical studies: prevalence of sarcomere variants in patients diagnosed with HCM
- 34%
- Population-based studies: P/LP sarcomere variants in the background population
- <1%
Gene-specific penetrance (family/clinical studies)
- MYL3
- ≈32%
- MYBPC3
- ≈55%
- TNNT2 and TNNI3
- ≈60%
- MYH7
- ≈65%
Age at HCM diagnosis (nonproband relatives, cascade screening)
- Mean age at HCM diagnosis
- 38 years (95% CI, 36%-40%)
Phenotypic conversion from subclinical to overt HCM (longitudinal family studies) · average of ≈8 years of follow-up
- Pooled conversion across all genes, from a mean of ≈16 years of age
- 15%
- Short-term conversion, MYBPC3
- ≈12%
- Short-term conversion, MYH7
- ≈23%
Original publication
Summarised from the published abstract; every number is checked against it