Cerebral palsy in siblings caused by compound heterozygous mutations in the gene encoding protein C
- 13 April 2010
- journal article
- case report
- Published by Wiley in Developmental Medicine and Child Neurology
- Vol. 52 (5), 489-493
- https://doi.org/10.1111/j.1469-8749.2010.03618.x
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.Keywords
This publication has 19 references indexed in Scilit:
- The protein C ω‐loop substitution Asn2Ile is associated with reduced protein C anticoagulant activityBritish Journal of Haematology, 2009
- Advances in understanding pathogenic mechanisms of thrombophilic disordersBlood, 2008
- Prothrombotic risk factors in children with hemiplegic cerebral palsyPediatrics International, 2007
- A report: the definition and classification of cerebral palsy April 2006Developmental Medicine and Child Neurology, 2007
- The cytoprotective protein C pathwayBlood, 2006
- Associations between inherited thrombophilias, gestational age, and cerebral palsyAmerican Journal of Obstetrics and Gynecology, 2005
- Symptomatic Ischemic Stroke in Full-Term NeonatesStroke, 2000
- Inherited prothrombotic states and ischaemic stroke in childhoodJournal of Neurology, Neurosurgery & Psychiatry, 1998
- Neonatal Purpura Fulminans Due to Homozygous Protein C or Protein S DeficienciesSeminars in Thrombosis and Hemostasis, 1990
- Diagnosis and treatment of homozygous protein C deficiency: Report of the working party on homozygous protein C deficiency of the subcommittee on protein C and protein S, international committee on thrombosis and haemostasisThe Journal of Pediatrics, 1989