Cerebral palsy appears to have a genetic component, with increased risk extending to third-degree relatives (first cousins), according to findings from a population-based cohort study.
These data "offer additional evidence that the underlying causes of cerebral palsy extend beyond the clinical management of delivery. However, the similar risks of cerebral palsy of co-twins of affected like-sex and unlike-sex twin pairs suggest that genetic influences are only part of a wide range of causes," the researchers concluded, noting that future studies should consider the possibility of genetic causes and genetic susceptibility to environmental causes.
Of over 2 million Norwegians born between 1967 and 2002 and included in the Medical Birth Registry of Norway, 3,649 were diagnosed with cerebral palsy, Dr. Mette C. Tollånes of the University of Bergen and her colleagues reported online July 15 in the British Journal of Medicine.
Individuals who had a twin with cerebral palsy had a 15.6-fold increase in the risk of cerebral palsy. Subsequent full or half siblings of a child with cerebral palsy had a 9.2-fold and 3.0-fold increase in the risk of cerebral palsy, respectively, and parents with cerebral palsy had a 6.5-fold increase in the risk of having an affected child, the investigators found (BMJ 2014 July 15 [doi:10.1136/bmj.g4294]).
Although the risk was lower than for first- and second-degree relatives, even those who had a first cousin with cerebral palsy were at a 1.5-fold increased risk of cerebral palsy, they said.
There was no evidence of a difference in the rate of transmission by affected mothers or fathers, and the risks seen in siblings and cousins were independent of the sex of the index case, Dr. Tollånes and her associates noted.
Prior studies have shown that, in addition to a number of risk factors in pregnancy and during the perinatal period – such as preterm delivery, multiple fetuses, birth asphyxia, and perinatal stroke – there also is a possible heritable component. In fact, a number of candidate genes and single nucleotide polymorphisms have been investigated to explain familial clustering of cerebral palsy, and some studies have extended the investigation to interactions with clinical factors and other genes.
Positive findings, however, have been difficult to replicate, the investigators said.
"We used data from a large population based cohort to ... shed light on patterns of inheritance," they wrote.
Although limited by a number of factors, including lack of information on cerebral palsy subtypes, an inability to identify cases with postneonatal causes, and a possible underestimation of recurrence risk because of the exclusion of those who didn’t survive past 3 years, the findings "suggest that cerebral palsy includes a genetic component, with a stronger recurrence among relatives with closer genetic relationship," Dr. Tollånes and her associates said.
This study was supported by grants from the University of Bergen; the Western Norway Regional Health Authority; and the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health. The authors reported having no disclosures other than support from these funding sources.