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This review summarizes the current insights on the genetic basis of cerebral palsy, discussing the contribution of single nucleotide polymorphisms (SNPs), copy number variants (CNVs), single gene mutations/ monogenic causes and epigenetic factors and indicating an important contribution of genetic factors to CP. Further studies, including CP animal models, are needed to increase our understanding of CP pathology, in order to pinpoint targets for future therapy development.

The genetic basis of cerebral palsy

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This review summarizes the current insights on the genetic basis of cerebral palsy, discussing the contribution of single nucleotide polymorphisms (SNPs), copy number variants (CNVs), single gene mutations/ monogenic causes and epigenetic factors and indicating an important contribution of genetic factors to CP. Further studies, including CP animal models, are needed to increase our understanding of CP pathology, in order to pinpoint targets for future therapy development.

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Synopsis of resource:

The best evidence in CP intervention today is still limited to controlling symptoms to some extent. This review article provides a comprehensive overview of how genomic information is being harnessed to improve our knowledge of etiology and pathophysiology of CP. The fairly constant incident rate of CP despite improved perinatal care, the fact that despite severe insults, some babies do not develop the motor sequelae, all point towards possible role of genetics in CP. Epigenetic mechanisms may influence the predisposition to CP pathology under environmental stressors. Next generation sequencing has helped identify some cases of monogenic CP and microarray studies have provided useful insights into CP neurobiology.

Heterogeneity plagues not just clinical presentation but also the CP genomics and research done so far is limited by small cohorts and lack of validation studies. This article gives a synopsis of the present and future of genetics in CP and the promise of identifying new targets for intervention.

Key learning outcomes

  • Genetic mutations may be responsible for nearly 30% cases of CP
  • Genomic microarray and next generation sequencing may yield a diagnosis in many cases of ‘unexplained CP’
  • Response to treatment may be predicted by characterisation of molecular subtypes in CP

Authors

Dr Fahey is the head of Pediatric Neurology at Monash Medical Center and a researcher specialising in neurogenetics. His research focuses on using neurogenetics to understand the causes of movement disorders and diseases of the muscle and nerve, including cerebral palsy. He is currently collaborating on research into treatments for Cerebral Palsy with researchers at the Ritchie Centre, part of the Monash Institute of Medical Research. In addition to working with the Ritchie Centre, Dr Fahey also collaborates on gene discovery research with Genetic Health Services Victoria and experts at the Alfred Hospital. He is also involved in the treatment of rare neuro-metabolic diseases with partners at the Royal Melbourne Hospital.

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