title: Childhood presentation of COL4A1 mutations.
abstract: OBJECTIVE
  To describe the clinical and radiological features of four new families with a childhood presentation of COL4A1 mutation.
  
  
  METHODS
  We 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 cases and, where possible, in affected family members.
  
  
  RESULTS
  The three male and one female index cases presented with recurrent childhood-onset stroke, infantile hemiplegia/spastic quadriplegia, and infantile spasms. Additional features such as congenital cataracts and anterior segment dysgenesis were present. Microcephaly and 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 porencephaly was present in cases with infantile hemiplegia, and a diagnosis of clinical stroke was supported by the presence of intracerebral haemorrhage. The age at diagnosis was between 1 year and 6 years for the children with presentation in infancy and 12 months after stroke in a 14-year-old male. Three new pathogenic mutations were identified in the COL4A1 gene.
  
  
  CONCLUSIONS
  COL4A1 mutations can present in children with infantile hemiplegia/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.
authors.affiliation: Department of Paediatric Neurology, Bristol Royal Hospital for Children, Bristol, UK.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Shah
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Rachel
authors.initials: R
authors.lastname: Kneen
authors.forename: Ming
authors.initials: M
authors.lastname: Lim
authors.forename: Nigel
authors.initials: N
authors.lastname: Osborne
authors.forename: Julia
authors.initials: J
authors.lastname: Rankin
authors.forename: Neil
authors.initials: N
authors.lastname: Stoodley
authors.forename: Marjo
authors.initials: M
authors.lastname: van der Knaap
authors.forename: Andrea
authors.initials: A
authors.lastname: Whitney
authors.forename: Philip
authors.initials: P
authors.lastname: Jardine
mesh_terms: D000293:Adolescent; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D024141:Collagen Type IV / Q000235:genetics*; D005124:Eye Abnormalities / Q000235:genetics; D005192:Family Health; D005260:Female; D006429:Hemiplegia / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D065708:Porencephaly; D012189:Retrospective Studies
chemical_list: C547475:COL4A1 protein, human; D024141:Collagen Type IV