Childhood presentation of COL4A1 mutations

Aim To describe the clinical and radiological features of four new families with a childhood presentation of COL4A1 mutation. MethodWe retrospectively reviewed the clinical presentation. Investigations included radiological findings and COL4A1 mutation analysis of the four cases. Affected family members were identified. COL4A1 mutation analysis was performed in all index casesand, where possible, in affected family members. Results The three male and one female index casespresented with recurrent childhood-onset stroke, infantilehemiplegia/ spastic quadriplegia, and infantilespasms. Additional features such as congenital cataracts and anterior segment dysgenesiswere present. Microcephalyand developmental delay/learning difficulties were present in three cases. Three cases had one or more family member affected in multiple generations, with a total of 11 such individuals identified. The clinical features showed a wide intrafamilial variation. Magnetic resonance imaging (MRI) showed bilateral white matter change in all cases, except in one mutation-positive family member. Unilateral or bilateral porencephalywas present in cases with infantilehemiplegia, and a diagnosis of clinical stroke was supported by the presence of intracerebral haemorrhage. The age at diagnosis was between 1year and 6years for the children with presentation in infancy and 12months after stroke in a 14-year-old male. Three new pathogenic mutations were identified in the COL4A1 gene. Interpretation COL4A1 mutations can present in children with infantilehemiplegia/quadriplegia, stroke or epilepsy, and a motor disorder. The presence of eye features and white matter change on MRI in childhood can help point towards the diagnosis. Once the diagnosis is made, a careful search can identify affected family members. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.