Ocular manifestations in the X-linked intellectual disability syndromes

Intellectual disability (ID), a common neurodevelopmental disorder characterized by limitations of both intellectual functioning and adaptive behavior, affects an estimated 1-2% of children. Genetic causes of ID are often accompanied by recognizable syndromal patterns. The vision apparatus is a sensory extension of the brain, and individuals with intellectual disabilities frequently have coexisting abnormalities of ocular structures and the visual pathway system. About one-third of the X-linked intellectual disability (XLID) syndromes have significant eye or ocular adnexa abnormalities that provide important diagnostic clues. Some XLID syndromes (e.g. Aicardi, cerebrooculogenital, Graham anophthalmia, Lenz, Lowe, MIDAS) are widely known for their characteristic ocular manifestations. Nystagmus, optic atrophy, and strabismus are among the more common, nonspecific, ocular manifestations that contribute to neuro-ophthalmological morbidity. Common dysmorphic oculofacial findings include anophthalmia, microphthalmia, hypertelorism, and abnormalities in the configuration or orientation of the palpebral fissures. Four XLID syndromes with major ocular manifestations (incontinentia pigmenti, Goltz, MIDAS, and Aicardi syndromes) are notable because of male lethality and expression occurring predominantly in females. The majority of the genes associated with XLID and ocular manifestations have now been identified.