Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel

Area of Science:

• Cardiovascular Genetics
• Clinical Lipidology
• Genetic Diagnostics

Background:

• Familial hypercholesterolemia (FH) is a common, inherited condition leading to high cholesterol and premature cardiovascular disease.
• Despite being treatable, FH remains significantly underdiagnosed globally.
• Current diagnostic approaches often miss cases, delaying crucial interventions.

Purpose of the Study:

• To assess the clinical utility and recommend the integration of genetic testing into standard care for Familial Hypercholesterolemia.
• To establish guidelines for genetic testing in suspected FH cases and their families.
• To explore the impact of genetic testing on diagnosis, risk stratification, and cascade testing.

Main Methods:

• Convened an international expert panel to review evidence on FH genetic testing.
• Evaluated the benefits of genetic testing, including diagnostic accuracy, risk assessment, and family screening.
• Defined key genes (LDLR, APOB, PCSK9) for FH genetic testing and considered phenotype-based gene selection.

Main Results:

• Genetic testing facilitates definitive FH diagnosis and identifies higher cardiovascular risk.
• Testing can improve initiation and adherence to lipid-lowering therapies.
• It enables effective cascade testing for at-risk relatives, leading to earlier diagnosis and treatment.

Conclusions:

• The Expert Consensus Panel recommends FH genetic testing as the standard of care for definite/probable FH and at-risk relatives.
• Widespread adoption is expected to increase diagnoses, improve cascade testing efficiency, and enable earlier, more accurate risk stratification.
• Integrating genetic testing is crucial for managing this common, yet underdiagnosed, genetic disorder.