BabyScreen+ newborn screening

Gene: LDLR

Green List (high evidence)

ClinGen: 'strong actionability' in paediatric patients.

For review as clinical manifestations are typically in adulthood. Statin therapy is recommended to be initiated as early as 8-12 years of age. However, there is also a severe, bi-allelic form with onset in early childhood.

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. In natural history studies, 50% of males and 25% of females with FH develop clinical CVD by age 50 years, but up to 10% can have severe premature CVD by 40 years of age. On average, individuals with HeFH experience their first coronary event at age 42, 20 years younger than the general population. 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.

Include bi-allelic disease in gNBS. Continue considering if and when mono-allelic disease should be included.

Created: 26 Sep 2022, 10:06 a.m. | Last Modified: 26 Oct 2022, 6:31 a.m.

Panel Version: 0.662

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hypercholesterolemia, familial, 1, MIM# 143890

Green List (high evidence)

Gene-disease association: well established

Onset: early childhood for biallelic, adolescence/adulthood for monoallelic

Treatment: diet, statins, surveillance

Created: 26 Sep 2022, 4:09 a.m. | Last Modified: 26 Sep 2022, 4:09 a.m.

Panel Version: 0.199

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
familial hypercholesterolemia