Additional findings_Paediatric

Gene: APOB

Green List (high evidence)

Well established gene-disease association.

Considered 'strongly actionable' by ClinGen, however, benefit in children is uncertain.

Elevated LDL-C levels can be detected from infancy and strongly predispose patients with FH to progressive atherosclerosis throughout childhood and premature CVD in adulthood. Although complications of atherosclerosis occur most commonly in individuals aged >50, the pathophysiological processes begin in childhood and are affected by additional risk factors: hypertension, diabetes, smoking, obesity, poor diet, and physical inactivity. By 12 years of age, children with FH have significant thickening of the carotid intima-media, and by 18 years have coronary stenosis.

Based on studies of individuals selected based on clinical criteria in the pre-statin era, untreated males are at 50% risk for a fatal or non-fatal coronary event by age 50 years, and women are at 30% risk by 60 years.

Treatable disorder: Statins have changed the prognosis of FH such that the rates of cardiovascular (CV) events are equal to the general population after 10 years of treatment. Other treatments, as well as lifestyle modification are also available and alter the natural history.

Statin therapy is recommended to be initiated as early as 8-12 years of age.

Relatively common, 1 in 200/500.

Created: 11 Nov 2022, 2:03 a.m. | Last Modified: 11 Nov 2022, 2:03 a.m.

Panel Version: 0.272

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Hypercholesterolaemia, familial, 2, MIM# 144010; Hypobetalipoproteinaemia 615558