Meta-Analysis of Penetrance and Systematic Review on Transition to Disease in Genetic Hypertrophic Cardiomyopathy.

age of onset cardiomyopathy, hypertrophic penetrance

Journal

Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763

Informations de publication

Date de publication:
09 Jan 2024
Historique:
pubmed: 6 11 2023
medline: 6 11 2023
entrez: 6 11 2023
Statut: ppublish

Résumé

Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants (P/LP) in genes encoding sarcomere proteins. Not all subclinical variant carriers will manifest clinically overt disease because penetrance (proportion of sarcomere or sarcomere-related P/LP variant carriers who develop disease) is variable, age dependent, and not reliably predicted. A systematic search of the literature was performed. We used random-effects generalized linear mixed model meta-analyses to contrast the cross-sectional prevalence and penetrance of sarcomere or sarcomere-related genes in 2 different contexts: clinically-based studies on patients and families with HCM versus population or community-based studies. Longitudinal family/clinical studies were additionally analyzed to investigate the rate of phenotypic conversion from subclinical to overt HCM during follow-up. In total, 455 full-text manuscripts and articles were assessed. In family/clinical studies, the prevalence of sarcomere variants in patients diagnosed with HCM was 34%. The penetrance across all genes in nonproband relatives carrying P/LP variants identified during cascade screening was 57% (95% CI, 52%-63%), and the mean age at HCM diagnosis was 38 years (95% CI, 36%-40%). Penetrance varied from ≈32% for The penetrance of P/LP variants is highly variable and influenced by currently undefined and context-dependent genetic and environmental factors. Additional longitudinal studies are needed to improve our understanding of true lifetime penetrance in families and in the community and to identify drivers of the transition from subclinical to overt HCM.

Sections du résumé

BACKGROUND UNASSIGNED
Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy and is classically caused by pathogenic or likely pathogenic variants (P/LP) in genes encoding sarcomere proteins. Not all subclinical variant carriers will manifest clinically overt disease because penetrance (proportion of sarcomere or sarcomere-related P/LP variant carriers who develop disease) is variable, age dependent, and not reliably predicted.
METHODS UNASSIGNED
A systematic search of the literature was performed. We used random-effects generalized linear mixed model meta-analyses to contrast the cross-sectional prevalence and penetrance of sarcomere or sarcomere-related genes in 2 different contexts: clinically-based studies on patients and families with HCM versus population or community-based studies. Longitudinal family/clinical studies were additionally analyzed to investigate the rate of phenotypic conversion from subclinical to overt HCM during follow-up.
RESULTS UNASSIGNED
In total, 455 full-text manuscripts and articles were assessed. In family/clinical studies, the prevalence of sarcomere variants in patients diagnosed with HCM was 34%. The penetrance across all genes in nonproband relatives carrying P/LP variants identified during cascade screening was 57% (95% CI, 52%-63%), and the mean age at HCM diagnosis was 38 years (95% CI, 36%-40%). Penetrance varied from ≈32% for
CONCLUSIONS UNASSIGNED
The penetrance of P/LP variants is highly variable and influenced by currently undefined and context-dependent genetic and environmental factors. Additional longitudinal studies are needed to improve our understanding of true lifetime penetrance in families and in the community and to identify drivers of the transition from subclinical to overt HCM.

Identifiants

DOI: 10.1161/CIRCULATIONAHA.123.065987 PMID: 37929589
pubmed: 37929589
doi: 10.1161/CIRCULATIONAHA.123.065987
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

107-123

Auteurs

Constantin-Cristian Topriceanu (CC)

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (C.-C.T., A.C.P., C.Y.H.). UCL Institute of Cardiovascular Science (C.-C.T., J.C.M., G.C.) and UCL MRC Unit for Lifelong Health and Ageing (G.C.), University College London, UK. Cardiac MRI Unit, Barts Heart Centre, West Smithfield, London, UK (C.-C.T., J.C.M.). The Royal Free Hospital, Centre for Inherited Heart Muscle Conditions, Cardiology Department, Hampstead, London, UK (G.C.).
ORCID: 0000-0001-5826-9617

Alexandre C Pereira (AC)

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (C.-C.T., A.C.P., C.Y.H.). UCL Institute of Cardiovascular Science (C.-C.T., J.C.M., G.C.) and UCL MRC Unit for Lifelong Health and Ageing (G.C.), University College London, UK. Cardiac MRI Unit, Barts Heart Centre, West Smithfield, London, UK (C.-C.T., J.C.M.). The Royal Free Hospital, Centre for Inherited Heart Muscle Conditions, Cardiology Department, Hampstead, London, UK (G.C.).
ORCID: 0000-0002-7782-5540

James C Moon (JC)

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (C.-C.T., A.C.P., C.Y.H.). UCL Institute of Cardiovascular Science (C.-C.T., J.C.M., G.C.) and UCL MRC Unit for Lifelong Health and Ageing (G.C.), University College London, UK. Cardiac MRI Unit, Barts Heart Centre, West Smithfield, London, UK (C.-C.T., J.C.M.). The Royal Free Hospital, Centre for Inherited Heart Muscle Conditions, Cardiology Department, Hampstead, London, UK (G.C.).

Gabriella Captur (G)

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (C.-C.T., A.C.P., C.Y.H.). UCL Institute of Cardiovascular Science (C.-C.T., J.C.M., G.C.) and UCL MRC Unit for Lifelong Health and Ageing (G.C.), University College London, UK. Cardiac MRI Unit, Barts Heart Centre, West Smithfield, London, UK (C.-C.T., J.C.M.). The Royal Free Hospital, Centre for Inherited Heart Muscle Conditions, Cardiology Department, Hampstead, London, UK (G.C.).
ORCID: 0000-0002-5662-0642

Carolyn Y Ho (CY)

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (C.-C.T., A.C.P., C.Y.H.). UCL Institute of Cardiovascular Science (C.-C.T., J.C.M., G.C.) and UCL MRC Unit for Lifelong Health and Ageing (G.C.), University College London, UK. Cardiac MRI Unit, Barts Heart Centre, West Smithfield, London, UK (C.-C.T., J.C.M.). The Royal Free Hospital, Centre for Inherited Heart Muscle Conditions, Cardiology Department, Hampstead, London, UK (G.C.).
ORCID: 0000-0002-7334-7924

Classifications MeSH