Clinical spectrum of type IV collagen (COL4A1) mutations: a novel genetic multisystem disease

Purpose of review This review dsecribes the clinical spectrum of a newly identified disorder related to COL4A1 gene mutations. COL4A1 encodes type IV collagen alpha 1 chain, a crucial component of nearly all basement membrane including vasculature, renal glomerule and ocular structures. Recent findings The human phenotypes are extremely variable between patients and between families, with disease onset as early as in the fetal period. COL4A1 mutations are responsible for a wide range of abnormalities affecting mainly the brain and the retinal vasculature, the anterior and posterior ocular structures and the renal glomerules. In the brain, intracerebral hemorrhage is the most frequent phenotype. It affects mainly young adults, children and more typically neonates. Mutated patients develop a diffuse small vessel disease of the brain as shown by a diffuse leukoencephalopathy on MRI. In the eye, patients may have retinal arteriolar tortuosities and retinal hemorrhages or anterior segment dysgenesis. Other phenotypes include intracranial aneurysms, porencephaly, infantile hemiparesis, muscle cramps, optic nerve dysgenesis and secondary glaucoma. There is in addition a specific phenotype called HANAC with constant nephropathy, muscle cramps and frequent intracranial aneurysms. Summary COL4A1 disorder is probably largely underestimated because of its multisystem and variable phenotype. In addition the whole spectrum of the phenotype is not yet known and there are many asymptomatic patients.