Familial hypercholesterolemia in adults: Overview
- Robert S Rosenson, MD
Robert S Rosenson, MD
- Section Editor — Lipids
- Professor of Medicine
- Mount Sinai School of Medicine
- Director, Cardiometabolic Disorders
- Mount Sinai Heart
- Paul Durrington, MD
Paul Durrington, MD
- Professor of Medicine
- Physician to Manchester Royal Infirmary
- University of Manchester
Familial hypercholesterolemia (FH) is the most common autosomal dominant genetic disease. The clinical syndrome (phenotype) is characterized by extremely elevated levels of low density lipoprotein cholesterol (LDL-C) and a propensity to early onset atherosclerotic cardiovascular disease. Homozygotes generally manifest disease in childhood. (See "Dyslipidemia in children: Definition, screening, and diagnosis", section on 'Familial hypercholesterolemia'.)
There are multiple definitions of FH in the literature. Some require the performance of genetic testing while others require very high levels of LDL-C with or without other clinical characteristics.
Other inherited lipid disorders are discussed separately. (See "Inherited disorders of LDL-cholesterol metabolism".)
This topic will focus on issues not related to the primary goal of therapy, which is to significantly lower LDL-C levels. Treatment is presented separately. (See "Familial hypercholesterolemia in adults: Treatment".)
Familial hypercholesterolemia (FH) is a genetic disease caused by functional mutations at one of three genetic loci. In the absence of genetic testing, which confirms one of these mutations, FH is defined based on clinical criteria. Many clinical definitions have been proposed with the following three representing the most commonly used :
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- GENETIC CONSIDERATIONS
- Homozygotes versus heterozygotes
- LDL receptor genetic defects
- Mutations in the PCSK9 gene
- Familial defective apolipoprotein B-100
- VARIATION IN LDL-C
- CLINICAL PRESENTATION
- CLINICAL SUSPICION
- Differential diagnosis
- INDICATIONS FOR REFERRAL
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS