Cerebral palsy (CP) is a group of disorders impacting movement, balance, and posture that manifest in early childhood. While historically attributed to non-genetic factors, current research indicates a notable role for genetic contributions in a subset of cases. Understanding these genetic influences is an evolving field, providing new perspectives on this complex condition.
Primary Causes of Cerebral Palsy
Cerebral palsy has long been associated with brain injury occurring at various stages of development. Brain damage during fetal development, such as from maternal infections like rubella or cytomegalovirus, or strokes in utero that interrupt blood supply, can lead to CP. Similarly, complications during birth, including oxygen deprivation or issues related to premature birth and low birth weight, are recognized factors.
Brain injuries shortly after birth can also contribute to the development of CP. These postnatal causes might include severe jaundice leading to kernicterus, brain infections like meningitis or encephalitis, or head trauma from accidents. While these environmental factors have traditionally been considered the primary causes for the majority of CP cases, the exact cause often remains unknown.
The Role of Genetics in Cerebral Palsy
While many cases of cerebral palsy are not inherited in a simple manner, genetic factors are increasingly recognized as contributors through various mechanisms. Recent studies suggest that inherited genetic causes could play a role in up to 25% of cases, a significant increase from earlier estimates of around 2%. This evolving understanding highlights the complex interplay of genetic and environmental influences.
Single Gene Mutations
Specific alterations in a single gene can lead to CP-like symptoms or directly contribute to CP, though these instances are relatively rare. These mutations can be inherited in autosomal dominant, autosomal recessive, or X-linked patterns.
Chromosomal Abnormalities
Larger-scale genetic changes, such as duplications or deletions of chromosomal segments, can also be associated with developmental brain issues that result in CP. These copy number variants (CNVs) can disrupt normal brain development and nerve cell connections, leading to conditions that manifest as CP.
Polygenic Inheritance and Genetic Predisposition
Beyond single gene mutations or chromosomal abnormalities, cerebral palsy can arise from the combined effect of multiple genes, each contributing a small influence. This polygenic inheritance means that an individual may inherit several genetic variations that, when interacting with environmental factors, increase their susceptibility to developing CP. This complex interaction can explain cases where no single clear genetic or environmental cause is identified.
Syndromic Cerebral Palsy
In some instances, cerebral palsy occurs as one component of a broader genetic syndrome, which includes other distinct symptoms. For example, conditions like Aicardi-Goutières syndrome, a rare genetic disorder, can present with spastic CP alongside other neurological features, emphasizing the importance of considering a wider syndromic diagnosis.
Genetic Testing and Counseling
Genetic testing can be considered for individuals with cerebral palsy, particularly when traditional risk factors are absent, or when there are other affected family members or unusual brain MRI findings. Tests such as chromosomal microarray (CMA) and whole exome sequencing (WES) are employed to identify genetic variants or chromosomal abnormalities. For instance, WES can reveal causative genetic variants in a notable percentage of CP patients, ranging from 15% to 34% in some studies.
Genetic counselors play a significant role in this process, helping families understand the purpose and limitations of genetic testing. They interpret complex test results, explain the implications of a genetic diagnosis, and provide support to families navigating these findings. While testing may not always yield a definitive answer, it can provide valuable information that refines the understanding of a child’s condition and may guide management.
Family Planning and Recurrence Risk
For families planning future pregnancies, understanding the genetic landscape of cerebral palsy can inform recurrence risk. If a specific genetic cause for CP is identified in one child, genetic counseling can offer a more precise assessment of the likelihood of future children being affected. For instance, if a de novo genetic variant (a new mutation not inherited from parents) is found, the recurrence risk for future children to the same parents is generally low, often less than 1%.
However, if the genetic change causing CP is inherited from one or both parents, the recurrence risk can increase significantly, potentially ranging from 25% to 50%, depending on the inheritance pattern. In such cases, options like prenatal diagnosis, which involves testing the fetus during pregnancy, or preimplantation genetic diagnosis (PGD), which screens embryos created through in vitro fertilization before implantation, may be discussed to help families make informed decisions for future pregnancies. For most CP cases linked to non-genetic factors, the recurrence risk for subsequent pregnancies remains low.