Is cerebral palsy (CP) genetic?

From the Guidelines

Cerebral palsy is typically not genetic, with the majority of cases resulting from brain damage or abnormal brain development before, during, or shortly after birth. While some cases of cerebral palsy may have genetic factors involved, the most common causes include oxygen deprivation during birth, infections during pregnancy, stroke in the baby's brain, traumatic head injury, or brain infections in early infancy 1. According to a 2023 systematic review and meta-analysis published in JAMA Pediatrics, the genetic diagnostic yield in cerebral palsy was similar to that of other neurodevelopmental disorders for which exome sequencing is recommended as standard of care 1. However, it's essential to note that only about 2% of cerebral palsy cases are believed to have a clear genetic cause, where specific gene mutations directly lead to the condition. Certain genetic factors may increase a child's susceptibility to brain injury or affect how the brain develops, potentially contributing to cerebral palsy when combined with environmental factors.

Key Points to Consider

• The complete causal path to cerebral palsy is unclear in approximately 80% of cases, but risk factors are often identifiable from history taking about conception, pregnancy, birth, and the postneonatal period 1.
• Genetic advances are likely to soon amend the diagnostic process, and early diagnosis does not preclude further specific etiological investigation 1.
• If there are concerns about cerebral palsy in a family, genetic counseling may be helpful, especially if there's a family history of the condition or if parents are planning future pregnancies.
• Early diagnosis and intervention with physical therapy, occupational therapy, speech therapy, and sometimes medications like muscle relaxants can significantly improve outcomes for children with cerebral palsy.

Recommendations for Practice

• Exome sequencing should be considered as a first-tier test for individuals with cerebral palsy, regardless of their comorbidities or risk factors 1.
• A comprehensive diagnostic evaluation, including clinical and neurological signs, should be performed to determine the underlying cause of cerebral palsy.
• Families with concerns about cerebral palsy should be referred to genetic counseling to discuss the potential risks and benefits of genetic testing.

From the Research

Cerebral Palsy and Genetics

• Cerebral palsy (CP) is a debilitating condition characterized by abnormal movement or posture, beginning early in development 2.
• Genetic factors of major effect contribute to the etiology of CP, with most copy number variants and small alterations of nucleotide sequence that cause CP arising as a result of de novo mutations 2.
• At least 4% of patients with typical CP have disease-causing CNVs, and at least 14% have disease-causing single nucleotide variants or indels 2.
• Mutations of many different genetic loci can produce a CP-like phenotype, highlighting the complexity of the genetic contributions to the condition 2.

Genetic Contributions to Cerebral Palsy

• Early family and twin studies and more recent genomic investigations demonstrate that genetic factors play a significant role in the etiology of CP 2.
• The importance of genetic variants of minor effect and of epigenetic modifications in producing a multifactorial predisposition to CP is less clear, requiring further research 2.
• Recognizing the specific cause of CP in an affected individual is essential to providing optimal clinical management, including genetic counseling and potential precision therapy 2.

Diagnosis and Management

• Trio exome sequencing with assessment of copy number or trio genome sequencing with bioinformatics analysis for single nucleotide variants, indels, and copy number variants is clinically indicated in the initial workup of CP patients, especially those with additional malformations or neurodevelopmental abnormalities 2.
• Management of CP involves neurological rehabilitation, diagnosis and management of co-morbidities, and a multidisciplinary approach involving various healthcare providers 3.