Clinical Domain Working Groups

Cerebral palsy (CP) is a neurodevelopmental disorder defined as “a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain; the motor disorders of CP are often accompanied by disturbances of sensation, perception, cognition, communication, and behavior, by epilepsy, and by secondary musculoskeletal problems.” CP is the most common major disabling motor disorder of childhood, with a prevalence of 1:500.

A growing body of evidence suggests that a significant proportion of CP is likely caused by rare genomic variants, including copy number variants and single nucleotide variants, similar to other neurodevelopmental disorders, such as intellectual disability, autism spectrum disorder, and epilepsy. Reported diagnostic yields using various platforms including chromosomal microarrays and exome sequencing in cohorts with CP range from 10 to 45%. Additional evidence for genomic contributions to the etiology of CP comes from case reports and series in which pathogenic single-gene abnormalities have been identified in individuals with CP. These early data suggest significant genomic heterogeneity and a vast underlying genomic landscape for CP, including multiple genes shared with other neurodevelopmental disorders, which requires expert gene curation to establish clinical validity, pathogenicity, and clinical utility to determine which genes are valid disease genes ready for clinical testing.

The gene list to be reviewed will be derived from genes marketed for clinical testing for CP, including Invitae Cerebral Palsy Spectrum Disorders Panel (265 genes, https://www.invitae.com/en/physician/tests/55004/) and GeneDx Cerebral Palsy Xpanded Panel (>1,000 genes, https://www.genedx.com/tests/detail/cerebral-palsy-xpanded-panel-1011), as well as the cerebral palsy gene list curated by PanelApp Australia (102 genes, https://panelapp.agha.umccr.org/panels/73/).