Late-Onset COL4A1 Mutation with Recurrent Ischemic and Hemorrhagic Strokes.

Introduction: Mutations in type IV collagen gene COL4A1 are identified as a cause of autosomal dominant cerebrovascular disease. We report an unusual late-onset presentation.

Case report: A 64-year-old male was found to have an ischemic stroke and diffuse white matter changes. Genetic testing revealed COL4A1 gene mutation of heterozygous Alu insertion at intron 16. Alu elements are known as "jumping genes," and Alu insertion is not previously reported in COL4A1 genetic syndromes. Our case has attributes consistent with a heritable leukoencephalopathy: (1) late-onset presentation, (2) intracerebral hemorrhages and microbleeds, (3) bilateral symmetrical leukoencephalopathy, (4) recurrence over a short period of time, (5) bilateral retinopathy, and (6) family history notable for brain aneurysm, kidney diseases, and early-onset stroke.

Conclusions: Although the majority of COL4A1 genetic syndromes featuring cerebral small vessel disease are in children, this case highlights a late-onset patient with key features of COL4A1 syndromes associated with a heterozygous Alu intronic insertion.