Strabismus in children with intellectual disability: part of a broader motor control phenotype?

Abstract Purpose Intellectual disability (ID) results from a heterogeneous group of disorders and affects 1-2% of children. ID frequently occurs in association with other clinical features such as seizures or malformations. We suspected that strabismus might also be unusually frequent in this population and that it might be associated with ID groups affecting motor control. Methods We reviewed phenotypic descriptors, extracted from medical records, for a heterogeneous series of 222 probands with ID who had been enrolled in a study of clinical application of exome sequencing. We estimated the frequency of strabismus and other common clinical features, and explored statistical associations between them. Data from Population Data British Columbia and Online Mendelian Inheritance in Man were also examined for confirmation of our observations. Results Strabismus had a higher prevalence among probands with ID than in the general population (odds ratio=5.46). Moreover, probands with both ID and strabismus were more likely to have problems affecting motor control than those with ID and no strabismus (odds ratio=2.84). Hypotonia was one of the most common motor control subgroups affecting the ID probands, and a frequent co-occurrence between strabismus and hypotonia was also observed (odds ratio=2.51). A literature review of the associated genes supported the association. There was no evidence for associations between strabismus and other frequent clinical features. Conclusion Strabismus is a frequent feature in individuals with ID. The frequent co-occurrence of strabismus and motor control phenotypes, in particular hypotonia, suggests that a common cerebellum mechanism or pathway may underlie these phenotypes.