Genetic Abnormalities May Cause Cerebral Palsy

For years it was thought that a difficult birth and other perinatal factors were the leading causes of cerebral palsy (CP), a group of disorders that can involve brain and nervous system functions such as movement, learning, hearing, seeing and thinking. Now, researchers at Geisinger Health System find that the majority of cerebral palsy causes may in fact be caused by genetic abnormalities.

Published in the The Lancet Neurology, Geisinger researchers find that CP - the most common physical disability of childhood - is probably caused by multiple genetic factors, similar to other neurodevelopmental disorders such as autism and intellectual disability. The paper suggests physicians should consider performing genetic testing when children present with CP and CP-like conditions.

“There is a widespread misconception that most cases of CP are caused by difficult delivery leading to birth asphyxia,” said Andres Moreno De Luca, M.D., research scientist at the Genomic Medicine Institute, Geisinger Health System, and lead author of the paper. “What we’re finding is a growing body of evidence that suggests mutations in multiple genes are responsible for CP. In fact, we suspect these genetic abnormalities may also be the cause of some difficult births to begin with.”

Despite substantial improvements in obstetric and neonatal care, the paper finds the worldwide prevalence of cerebral palsy has remained stable at 2 to 3 per 1,000 livebirths for more than 40 years. Inadequate oxygen supply to fetuses, known as birth asphyxia, remains the most studied factor associated with CP, though electronic fetal monitoring and other technologies have been developed to detect fetal distress.

“What we’re finding is even though more preventative efforts have been put in place, like fetal monitoring, the incidence of CP has not decreased,” said David Ledbetter, Ph.D., chief scientific officer, Geisinger Health System. “We’ve seen a five-fold increase in the rate of caesarean sections, which are done in part to avoid potentially difficult delivery, and again, the CP rates remain steady. These findings lead us to believe genetics play a much bigger role than previously thought.”

Genetic factors play a part in cerebral palsy both as part of a multi causal pathway and as a sole source of damage. In cultures where consanquinous marriage is common or in smaller isolated areas, genetic origins of cerebral palsy can surface.

“…the pathological effect of later factors can be dependent on the presence of earlier factors while not being a direct result of them. For example, Morton et al., (1991) reported a series of cases of cerebral palsy among the Amish of North America. These were neurologically damaged during an infection in infancy, but the pathological effect of the infection was dependent on their genetically inherited metabolic defect.” (Stanley et al., p 6-7)

Studies report that in families where cerebral palsy has occurred, the chances of it happening again are higher when compared with controls. When twins are involved, if one of the twins dies in utero or after birth, the chances that the second twin will contract CP increases whether they identical twins or not. Yet it has been estimated that if the twins are same sex, monochorionicity is a factor increasing the chance that both twins will suffer CP.