title: Cerebral palsy in siblings caused by compound heterozygous mutations in the gene encoding protein C.
abstract: We report two sisters with extensive bilateral periventricular haemorrhagic infarction (PVHI) causing cerebral palsy (CP). The older sister presented at 20 months with cortical visual blindness, spastic diplegia, and purpura fulminans. The younger sister presented aged 3 days old with apnoeas and multifocal seizures. She subsequently had global developmental delay, cortical visual blindness, spastic quadriplegia, epilepsy, and purpura fulminans at age 2 years. Neuroimaging of both siblings showed bilateral PVHI consistent with bilateral cerebral intramedullary venous thrombosis occurring at under 28 weeks' gestation for the older sister and around time of birth for the younger sister. At latest follow-up, the older sister (13y) has spastic diplegia at Gross Motor Function Classification System (GMFCS) level II, and the younger sister (10y) has spastic quadriplegia at GMFCS level IV. Both sisters showed partial quantitative reduction in plasma protein C antigen and severe qualitative reduction in plasma protein C anticoagulant activity. They were heterozygous for two independent mutations in the protein C gene (PROC). There was no other risk factor for CP. To our knowledge, this is the first family reported with compound heterozygous PROC mutations as the likely genetic cause of familial CP. This report adds to the list of known monogenic causes of CP.
authors.affiliation: Department of Paediatric Neurology, Bristol Royal Hospital for Children, Bristol BS2 8AE, UK.
authors.forename: Choong Y I
authors.initials: CY
authors.lastname: Fong
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Mumford
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Likeman
authors.forename: Philip E
authors.initials: PE
authors.lastname: Jardine
mesh_terms: D019575:Blindness, Cortical / Q000209:etiology / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000235:genetics / Q000473:pathology; D002544:Cerebral Infarction / Q000150:complications / Q000235:genetics / Q000473:pathology; D002547:Cerebral Palsy / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002552:Cerebral Ventricles / Q000473:pathology*; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D009154:Mutation; D011486:Protein C / Q000235:genetics* / Q000276:immunology; D012307:Risk Factors; D012720:Severity of Illness Index; D035781:Siblings
chemical_list: D011486:Protein C