Col4A1 and A2 mutation disorders, a clinical-radiological case series from India

COL4A1 and COL4A2 mutations have been well recognized as cause of basement membrane disease in humans involving various vasculatures in the brain, eyes, kidneys, skin and muscle. The presentation can be mild to severe and from fetus to adulthood. As genetic testing advances with newer technologies, diagnosing affected individuals has become more cost effective and reliable. There have been few reports of individuals of Indian origin with COL4A1 mutations published. However there are no reports of COL4A2 patients so far. We describe the largest case series of 3 COL4A1 and 3 COL4A2 paediatric patients from different institutions of India confirmed to have a mutation. Also we add to the spectrum of neurological and radiological findings seen in children with COL4A1. All 3 patients with COL4A1 from our series presented with epilepsy, 2 of them had infantile spasms. 1 of the 3 cases had cataract. Amongst the COL4A2 cases 3/3 had epilepsy with one having refractory epilepsy and one presenting with focal status epilepticus. None had cataracts. A variety of new and previously described point mutations were detected. A range of MRI Brain findings including white matter change, gliosis and calcification ( suggestive of previous stroke ) and neuromigration disorders were detected.
Keywords: COL4A1, COL4A2, stroke, epilepsy