Cerebral Palsy Meta-Analysis Points to Potential Diagnostic Benefits of Exome Sequencing, Chromosomal Microarrays

A Boston Children's Hospital-led team reporting in JAMA Neurology presents findings from a meta-analysis study looking at exome sequencing and chromosomal microarray approaches for finding molecular contributors to cerebral palsy (CP). Based on data from 15 cohorts that included more than 2,400 participants, for example, the researchers saw a diagnostic yield of around 23 percent overall for cases evaluated by exome sequencing, though the yield increased in sets of patients with "cryptogenic" forms of the disease. On the chromosomal microarray side, meanwhile, they found that copy number alterations uncovered with that approach made it possible to diagnose 5 percent of the 294 cases considered. "For individuals with cryptogenic CP or noncryptogenic CP with red flags concerning for a genetic disorder, if clinical/radiologic assessment does not suggest a specific cause, we propose using trio [exome sequencing] as a first-line sequencing test followed by [chromosomal microarray] (if whole-genome sequencing is not available at onset," the authors suggest, adding that "[w]e also recommend periodic clinical reevaluation and reanalysis of whole-genome sequencing or [exome sequencing] data for those with no molecular diagnosis identified."