Aniridia-intellectual disability syndrome

Aniridia-intellectual disability syndrome, also known as aniridia-cerebellar ataxia-intellectual disability syndrome or Gillespie syndrome, is a rare genetic disorder characterized by the combination of partial or total absence of the iris (aniridia), intellectual disability, and cerebellar ataxia. The condition is present from birth and affects multiple body systems, most notably the eyes, the brain, and the nervous system. The ocular features include bilateral partial aniridia, which is often described as having a fixed, dilated pupil with a scalloped or irregular edge, distinguishing it from the more common PAX6-related isolated aniridia. Affected individuals typically have non-progressive cerebellar ataxia, which causes difficulties with balance, coordination, and fine motor skills. Intellectual disability ranges from mild to moderate. Additional features may include hypotonia (reduced muscle tone) in infancy and delayed motor development. Gillespie syndrome can be caused by biallelic pathogenic variants in the ITPR1 gene (encoding inositol 1,4,5-trisphosphate receptor type 1), which plays a critical role in cerebellar function and development. Both autosomal recessive and autosomal dominant (de novo) inheritance patterns have been described. There is currently no cure for this condition. Management is supportive and multidisciplinary, involving ophthalmologic care (including monitoring for glaucoma and use of corrective lenses or artificial pupil devices), physical and occupational therapy for ataxia, and educational support for intellectual disability. Regular developmental assessments and neurological follow-up are recommended.

Common questions about Aniridia-intellectual disability syndrome