Genomic Architecture and Cascade Screening Gaps in Hypertrophic Cardiomyopathy: A Real-World Analysis

Area of Science:

• Cardiovascular Genetics
• Medical Diagnostics
• Genomic Medicine

Background:

• Hypertrophic cardiomyopathy (HCM) is a genetically diverse condition.
• Recent insurance coverage for HCM genetic testing in Japan has increased variant detection.
• Current funding limitations restrict testing to symptomatic individuals.

Purpose of the Study:

• To evaluate institutional genetic testing outcomes in HCM patients.
• To identify factors associated with pathogenic variants.
• To assess the follow-up and cascade screening of at-risk relatives.

Main Methods:

• Retrospective analysis of individuals undergoing genetic testing for HCM (Oct 2022 - June 2025).
• Collection of data on molecular results, family history, and cascade screening.
• Statistical analysis using R software.

Main Results:

• Pathogenic or likely pathogenic variants (PV or LPV) were found in 39% of 33 probands.
• The PV or LPV group was younger (median 34 vs. 59 years) and had a stronger family history (77% vs. 20%).
• Only 3 relatives underwent cascade screening, with 2 testing positive and starting cardiac surveillance.

Conclusions:

• Actionable genetic results were achieved, but cascade screening uptake remains low.
• Improved communication and systemic support are crucial for family-based testing.
• Facilitating cascade screening is essential for advancing precision medicine in HCM.