Cerebral palsy (CP) is a group of disorders that affect a person’s ability to move and maintain posture, appearing during early childhood. Historically, the understanding of CP largely focused on complications around the time of birth, such as a lack of oxygen. However, contemporary research is increasingly revealing that genetic factors play a significant role in many cases. This shift in understanding challenges long-held assumptions and opens new avenues for diagnosis and support.
The Evolving Understanding of Cerebral Palsy Causes
For many years, cerebral palsy was believed to stem almost exclusively from events during the perinatal period, such as oxygen deprivation, physical trauma during delivery, or maternal infections.
Modern research has brought a more comprehensive perspective, indicating that a substantial portion of CP cases have an underlying genetic basis. Studies suggest that genetic causes contribute to a significant percentage of diagnoses, with estimates ranging from 14% to over 30% of cases. This new understanding does not dismiss other causes but integrates genetics as a significant contributing factor, sometimes acting alone or increasing a child’s vulnerability to other risk factors like prematurity or infection. For instance, some babies who experience birth asphyxia and are diagnosed with CP may have improper brain development due to underlying genetic variants, rather than solely a lack of oxygen.
How Genetics Contribute to Cerebral Palsy
Genetic variations can lead to cerebral palsy through several distinct biological pathways. One pathway involves genes that provide the instructions for brain formation and development. If there is a change or “typo” in one of these genes, it can disrupt the normal wiring and structure of the brain, leading to the motor control difficulties seen in CP. For example, genes like FBXO31 and RHOB have been identified where mutations alone can be sufficient to cause cerebral palsy by impacting brain circuitry during early development.
Another way genetic factors contribute is by increasing the brain’s susceptibility to injury. Some genetic issues do not directly cause CP but make the developing brain more vulnerable to external stressors. A genetic variant might, for instance, affect how brain cells respond to stress or minor drops in oxygen, meaning an event that might not harm another fetus could cause significant damage in a genetically predisposed child.
Genes related to other bodily systems can also indirectly influence brain health and contribute to CP. For example, genetic factors affecting blood clotting mechanisms could increase the risk of a perinatal stroke, which in turn can lead to brain damage and CP. Genes involved in metabolic disorders, which impact how the body processes substances, can also affect brain function and development.
Identifying Genetic Factors in Cerebral Palsy
Identifying a genetic link in cerebral palsy often involves advanced genetic testing. Whole-exome sequencing (WES) is a common approach used to find these genetic factors. This test involves reading the protein-coding regions of an individual’s genes to look for variations or “typos” that might explain a condition. Whole-genome sequencing, which examines all of an individual’s DNA, can also be employed for a more comprehensive analysis.
Genetic testing is typically recommended when there are no clear environmental causes for CP, when other co-occurring conditions like intellectual disability or epilepsy are present, or if there is a family history of similar neurological issues. Studies have shown that WES can identify a genetic cause in a significant percentage of CP cases, with diagnostic yields ranging from 7% to 35%, especially in patients without known risk factors.
Despite these advancements, there are limitations to current genetic testing. Even with comprehensive sequencing, a genetic cause is not always identified, as not all causative genes are currently known. A “negative” result does not definitively rule out a genetic contribution, given the ongoing discovery of new genes and the complex nature of genetic interactions.
Implications for Families and Future Planning
Discovering a specific genetic cause for cerebral palsy can provide families with much-needed answers, often ending a long and challenging diagnostic journey. This clarity can alleviate feelings of guilt or uncertainty about what caused their child’s condition. A genetic diagnosis can also connect families with others who have the same genetic finding, fostering a sense of community and shared understanding.
A genetic diagnosis also provides valuable information regarding the recurrence risk for future pregnancies. The likelihood of having another child with CP depends on the specific gene identified and its inheritance pattern, which can be determined through genetic testing. For instance, if the genetic change is de novo (not present in either parent), the recurrence risk for future children is generally low, less than 1%. However, if the genetic change is inherited from one or both parents, the risk can increase significantly, to 25% or even 50% for future children.
Genetic counseling plays an important role in helping families navigate this complex information. A genetic counselor is a healthcare professional who explains test results, discusses inheritance patterns, and clarifies what the diagnosis means for the child’s health management and the family’s future planning. They provide support and guidance, ensuring families understand the implications of a genetic diagnosis and make informed decisions about medical care and family planning.