Cerebral palsy and genomics: an international consortium (2018)

Historically it was believed that the primary cause of cerebral palsy (CP) was intrapartum complications, predominantly birth asphyxia. However, epidemiological studies have suggested that most cases are associated with other clinical risk factors1 including preterm birth, presence of congenital anomalies, fetal growth restriction, placental pathology, and an altered fetal inflammatory response. It has been hypothesized that much of the unknown pathophysiology of CP may be genetically caused.2, 3 Medical practice is increasingly embracing genomics, enabling stratification of disorders into more accurate diagnoses to refine prognosis, better guide management, and personalize therapeutic interventions. Accumulating evidence of the role of genetic variation in CP aetiology suggests that individuals with CP should undergo genomic testing as part of their diagnostic workup.2, 3 An international consortium provides a platform for genomic research success4 by increasing sample size and statistical power, enabling replication, facilitating multidisciplinary functional validation, and establishing common computational biology pipelines to harmonize workflows. In March 2017, scientists and clinicians working on CP genomics gathered in Adelaide, Australia, and supported a formalized, multidisciplinary, open international collaboration for CP, leading to the formation of the International Cerebral Palsy Genomics Consortium (ICPGC). The primary goals of the ICPGC are to facilitate the collection, analysis, interpretation, and dissemination of CP genomic findings and associated clinical data to maximize their research and translational value. To address these goals, the ICPGC is developing a platform to integrate genotype, phenotype, and imaging data as well as biobank sample availability. There is no uniform way to present these data; however, a focused effort for interoperability through global unique identifiers, recognized standards, and common data elements is crucial. Data harmonization will guarantee reproducibility and high-performance computing centre independence. While the primary aim is to act as a central resource for CP genomics researchers, eventual sharing through federation with other existing databases will enhance discovery. To accelerate and foster the discovery of genomic variants relevant to CP, precise and deep phenotyping will be critical. This can be accomplished with the use of internationally accepted clinical (e.g. Surveillance of Cerebral Palsy in Europe) and functional (e.g. Gross Motor Function Classification System; Manual Ability Classification System; Communication Function Classification System; or Eating and Drinking Ability Classification System) terminologies. To this end, a semantic language enriched with ICD-10 (International Statistical Classification of Diseases and Related Health Problems 10th Revision), HPO (Human Phenotype Ontology), and other nosology systems, as well as functional descriptions which have proven successful in application for other disease domains, especially rare diseases,5 will be used and further developed. We invite all researchers in the field, who have data and/or samples from existing or ongoing studies, to join ICPGC. We also welcome interest from advocacy groups and clinicians that care for large CP populations; clinical-research-community partnerships will be critical for timely, coordinated, and transformative advances. The 2nd ICPGC meeting will be held in the Henan Province, China on April 12th to 15th, 2018 (http://icpgc2018.medmeeting.org/en). Those investigators who have a shared interest in contributing data to, or collaborating with the ICPGC should visit our website (www.icpgc.org). Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.