Fusiform dilatation of the ascending aorta and outpouching of the left A2 anterior cerebral artery segment in COL4A1 -related disorder.

backgroundCOL4A1 encodes the alpha-1 chain of type IV collagen, which plays a crucial role in vascular basement membranes. The clinical manifestations of COL4A1-related disorders are yet to be fully defined. There is increasing evidence that COL4A1 may play crucial roles across the vascular system.

methodsWe studied a 71-year-old man with a novel splice acceptor variant, COL4A1 [NM_001845.6] c.1466-1G > C. Clinical, radiological (including comprehensive imaging of the brain as well as chest and abdomen), and genetic assessments were performed.

resultsHis medical history included fusiform dilatation (4.2 cm) of the ascending thoracic aorta, hearing loss, adrenal and pulmonary nodules, mild splenomegaly, and gallstones. Imaging showed fusiform dilatation (4.2 cm) of the ascending thoracic aorta and concomitant outpouching of the left A2 anterior cerebral artery in the patient in the setting of the heterozygous likely pathogenic splice site variant, COL4A1 c.1466-1G > C. Consistent with a diagnosis of COL4A1-related disorder, multiple cystic bilateral renal lesions were noticed on abdominal imaging. Magnetic resonance imaging of the brain also showed findings consistent with cerebral vasculopathy with scattered bilateral punctate T2/FLAIR hyperintensities within the supratentorial and pontine white matter.

conclusionOur observations support the growing body of evidence suggesting crucial roles for COL4A1 in vascular homeostasis including medium sized vessel cerebral vasculopathy and aortopathy.