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Genetic testing for familial hypercholesterolemia (FH) should become the standard of care for definite or probable cases and their at-risk relatives, recommended a consensus group convened by and including representatives of the Familial Hypercholesterolemia Foundation.

Testing should include the genes encoding the LDL receptor (LDLR), apolipoprotein B (APOB), and PCSK9, with other genes considered for certain patient phenotypes, Amy Sturm, of the Genomic Medicine Institute in Danville, Pennsylvania, and colleagues wrote in the .

The group recommended offering genetic testing for FH to any child or adult with strong clinical index of suspicion for it due to clinical or family history or both. This could include LDL persistently ≥160 mg/dL for children or 190 mg/dL for adults without apparent secondary cause when there is a first-degree relative similarly affected, or with premature coronary artery disease, or where family history is not available.

Testing should be offered even in the absence of a positive family history for persistent LDLs of at least 190 mg/dL for children or 250 mg/dL for adults without an apparent secondary cause of hypercholesterolemia. Those recommendations were deemed class IIa.

First-degree relatives should, with a class I recommendation, be offered genetic testing for the specific variant or variants identified in the FH proband, and to the second-degree relatives if the first-degree relatives aren't available or don't want to be tested.

Other groups that may be considered for FH genetic testing (and its accompanying genetic counseling), with a IIb recommendation, were:

• Children with LDL persistently ≥160 mg/dL with a parent ≥190 mg/dL or a family history of high cholesterol and premature coronary disease
• Adults with no pretreatment LDL measures but a personal history of premature coronary disease and family history of both hypercholesterolemia and premature coronary disease
• Adults with LDL persistently ≥160 mg/dL LDL with a family history of hypercholesterolemia and either a personal or family history of premature coronary disease

FH genetic testing is "underutilized" in the U.S., Strum's group argued, pointing to a rate of just 3.9% in the CASCADE FH Registry among people with a clinical diagnosis.

FH can be diagnosed from clinical findings alone, but genetic testing allows definitive molecular diagnosis and is discussed in the and by other groups, the document noted. Cascade testing of relatives has Tier 1 classification by the CDC Office of Public Health Genomics.

Knowing the genes involved allows for prognosis and risk stratification and has actually been shown to improve uptake of lipid-lowering therapy, adherence, and thus degree of lipid lowering, they pointed out.

FH isn't ruled out when genetic testing for the main variants involved (LDLR, the region of APOB encoding the LDLR ligand, and PCSK9) doesn't turn up a pathogenic variant, as there could be undetected or as-yet-unknown pathogenic variants, for instance, they added.

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