Strabismus in Genetic Syndromes: A Review

Strabismus is a feature of many genetic syndromes, with highly variable penetrance. The congenital cranial dysinnervation disorders (CCDDs) result in paralytic strabismus, with limited eye movements. CCDDs result from either deficits in differentiation of the cranial motor neuron precursors or from abnormal axon guidance of the cranial nerves. Although most individuals with comitant strabismus are otherwise healthy, strabismus is a variable feature of many genetic syndromes, most commonly those associated with intellectual disability. We review 255 genetic syndromes in which strabismus has been described and discuss the variable penetrance. The association with intellectual disability and neurological disorders underscores the likely neurological basis of strabismus, but the variable penetrance emphasises the complexity of strabismus pathophysiology. The syndromes described here mostly result from loss of function or change in function of the responsible genes; one hypothesis is that nonsyndromic strabismus may result from altered expression or regulation of the same genes.