Definition

Familial hypercholesterolemia (FH) is a lipid metabolism disorder caused by disruptions in the LDL receptor pathway (LDLR, APOB, PCSK9 genes) that produces markedly elevated LDL cholesterol from birth. The heterozygous form has a population frequency of about 1 in 250; untreated heterozygotes develop early coronary artery disease, and homozygotes develop severe atherosclerosis in childhood. Clinical findings may include xanthomas, arcus cornea, and early myocardial infarction.

Gene/region examined

APOA2 - Exon 1, APOA2 - Exon 2, APOA2 - Exon 3, APOA2 - Exon 4

Method

Sequence analysis

Accepted sample types

EDTA blood, AF, CVS

Inheritance

Inherited, autosomal dominant (LDLR and APOB variants); PCSK9-related forms are also autosomal dominant, but PCSK9 loss-of-function variants are protective while gain-of-function variants are disease-causing.

Related Tests

Inheritance Patterns

Describes how a genetic condition is passed on within a family. There are five main patterns

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Carrier (Heterozygous / Homozygous)

Why it matters: In autosomal recessive inheritance, when each parent is a carrier (while both appear healthy), the chance of their child being born with the disease is 25% in each

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VUS (Variant of Uncertain Significance)

This is the situation where the test has detected a change in the DNA, but the role of this change in the development of disease is unconfirmed.

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How to Read a Genetic Test Result (Positive / Negative / VUS)

A genetic test result falls into three main categories

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Types of Genetic Tests

A genetic test is a type of medical test that detects changes in genes, chromosomes or proteins. Today there are more than 77,000 genetic tests available.

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