Introduction: Cerebral palsy (CP) is an "umbrella term" for motor disability diagnosed in childhood, which is caused by various brain injuries. Genomic rearrangements (GRs) are micro-deletions/duplications that were reported in children with neurodisabilities. We investigated the prevalence and characteristics of GRs in individuals for whom the etiology of CP is unknown, termed 'cryptogenic CP'.

Methods: 51 participants, age 10·3±7·7 years, with non-progressive pyramidal and/or extra-pyramidal signs since infancy and no identified etiology were enrolled. GRs were tested using Affymetrix platform and classified as: pathogenic GRs, likely pathogenic, likely benign or no GRs.  Main outcome measures were: positive (pathogenic and likely pathogenic GRs) or negative (likely benign and no GRs) findings.

Results: 38 GRs were found in 26/51 (51%) participants, most of which were considered positive (11/26 pathogenic and 5/26 likely pathogenic versus 10/26 likely benign) and were not previously reported to cause motor disability (12/16). Multiple GRs and de-novo findings were more common in the positive GRs group than in the negative group (p<0.001 and p=0·095 respectively). Most GRs in individuals with a relative with a significant neurological disorder (n=6/9) were de-novo. Dysmormphic features and non- motor comorbidities were more prevalent in individuals with significant/positive GRs (p=0.01 and p=0.03 respectively).

Conclusion:  GRs are common in individuals with cryptogenic CP. They are more likely to be multiple and de-novo even in families with another effected member. This useful test should be performed in individuals with CP of unknown etiology.