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