BabyScreen+ newborn screening

Gene: COL4A5

Green List (high evidence)

Well established gene-disease association.

Natural history: In males, truncating variants in COL4A5 are associated with an earlier age at onset of kidney failure; risk of ESRD before age 30 is estimated as 90% for large rearrangements and pathogenic nonsense and frameshift variants, 70% for splice variants, and 50% for missense variants. In males, progressive SNHL is usually present by late childhood or early adolescence, and interior lenticous typically becomes apparent in late adolescence or early adulthood. In females, renal disease ranges from asymptomatic disease to lifelong microhematuria to renal failure at a young age. In females, progressive SNHL is typically later in life, lenticonus may not occur, and central retinopathy is rare.

Assessed as 'strongly actionable' in paediatric patients by ClinGen.

Treatment: ACE inhibitors alter long-term outcomes.

Males with XLAS are recommended to be treated with ACEi at diagnosis (if older than 12-24 months), even before the onset of proteinuria. Guidelines differ slightly for the initiation of treatment in females with XLAS; one guideline recommends initiation of treatment at onset of microalbuminuria while a second recommends initiation at onset of microalbuminuria, hypertension, or renal impairment.

Created: 9 Nov 2022, 1:23 a.m. | Last Modified: 27 Dec 2022, 12:39 a.m.

Panel Version: 0.1681

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Alport syndrome 1, X-linked, MIM# 301050