High familial risks for cerebral palsy implicate partial heritable aetiology
Kari Hemminki1, Xinjun Li, Kristina Sundquist
1Division of Molecular Genetic Epidemiology, German Cancer Research Centre, Heidelberg, Germany. k.hemminki@dkfz.de
Insights
Familial cerebral palsy (CP) is rare, but recurrence risk is significantly higher for subsequent children, especially twins. This suggests a potential genetic component influencing CP development.
Area of Science:
- Neurology
- Genetics
- Pediatrics
Background:
- Cerebral palsy (CP) is the leading cause of severe childhood disability.
- The etiology of CP remains largely unknown.
- Limited data exists on the familial aggregation of CP.
Purpose of the Study:
- To investigate familial risks and recurrence rates of cerebral palsy.
- To explore the potential contribution of heritable factors in CP.
Main Methods:
- Utilized a Swedish nationwide database linking Multigeneration Register and Hospital Discharge Register (1987-2001).
- Calculated standardized hospitalization ratios (SHRs) for siblings of CP patients.
- Analyzed familial risks in singleton and twin sibling pairs.
Main Results:
- Familial CP accounted for 1.6% of all cases.
- Recurrence risk for a second affected child was 4.8-fold higher.
- Risk increased significantly for twins (29-fold) and specific CP subtypes (hemiplegia, diplegia, quadriplegia).
- High familial risks suggest a contribution from heritable factors.
Conclusions:
- Familial risks for cerebral palsy are substantial, particularly in twins and specific subtypes.
- Heritable factors likely play a role in CP etiology.
- Further molecular studies on affected sibling pairs are warranted to identify susceptibility genes.
Abstract:
Cerebral palsy is the commonest cause of severe childhood disability, the aetiology of which is largely unknown. Data on familial aggregation of cerebral palsy are very limited. We defined familial risks for siblings who were hospitalised because of cerebral palsy in Sweden. A nationwide database for neurological diseases was constructed by linking the Multigeneration Register to the Hospital Discharge Register for the years 1987-2001. Standardised hospitalisation ratios (SHRs) were calculated for affected singletons and twins by comparing them with siblings who had no cerebral palsy. A total of 3997 patients were recorded with cerebral palsy. Familial cerebral palsy was uncommon, and it accounted for 1.6% of all cerebral palsy cases. However, for parents who had had one affected child the risk of recurrence in another child was considerably increased. Parents of one affected child had a 4.8-fold risk of having a second affected child, and where the siblings were twins, the risk was 29-fold. These familial risks were particularly high in some clinical subgroups: 17-25 in singletons and 37-155 in twins, including hemiplegia, diplegia and quadriplegia. The remarkably high familial risks are difficult to explain without some contribution of heritable factors. The lack of discordant pairs may suggest that heritable factors are disorder type-specific. Affected concordant sibling pairs should be subjected to molecular studies aiming at identifying the susceptibility gene.
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