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Aniridia - cerebellar ataxia - intellectual disability

ORPHA1065
Synonym(s) Gillespie syndrome
Prevalence <1 / 1 000 000
Inheritance Autosomal recessive
Age of onset Infancy
Neonatal
ICD-10 -
OMIM
UMLS
  • C0431401
MeSH -
MedDRA -

Summary

Aniridia - cerebellar ataxia - intellectual disability, also known as Gillespie syndrome, is a rare congenital disorder characterized by the association of partial bilateral aniridia with non progressive cerebellar ataxia, and intellectual disability.

To date, less than 30 patients have been reported in the literature.

Aniridia is visible at birth as fixed dilated pupils and is associated with photobia. It can be accompanied with additional ocular findings such as foveal, patchy iris and/or optic nerve hypoplasia (see this term) that reduce the visual acuity, nystagmus, ptosis, strabismus, retinal hypopigmentation and/or pigmentary macular changes. Cataract and corneal opacities are never observed. Non progressive cerebellar ataxia is associated with delayed developmental milestones and hypotonia visible from the first year of life, gait and balance disorders with incoordination, intention tremor, and scanning speech. Intellectual disability is variable. Mild facial dysmorphic features may be observed such as high forehead, hypertelorism, epicanthic folds, depressed nasal bridge with anteverted nostrils, and thin upper lip. The cases referred to as atypical Gillespie syndrome correspond to the cases showing a more complex phenotype associating additional ocular findings and a mild dysmorphic face.

The etiology is unknown. Some atypical cases have been linked to mutations in the PAX6 gene (11p13) encoding a transcriptional regulator expressed in ocular, cerebral, olfactory, and pancreatic tissues. A case has also been reported due to a de novo translocation of chromosome X and 11 t(X;11) (p22.32;p12) but with no involvement of the PAX6 gene.

A presumptive diagnosis can be made in the first months of life: from slit lamp examination, the pupil border of the iris typically shows a scalloped 'festooned' edge with iris strands extending onto the anterior lens surface at regular intervals. In many cases, neuroimaging studies (CT scan, MRI) show cerebellar hypoplasia or atrophy, especially of the vermis, with occasionally white matter changes, diffuse atrophy of the cerebral hemispheres, and brainstem and frontal cortical atrophy.

Differential diagnosis includes Marinesco-Sjögren syndrome (see this term) in which congenital cataract is present, besides cerebellar ataxia and intellectual disability, and also aniridia (see this term).

Sporadic and familial cases have been observed. Although some families are compatible with autosomal dominant inheritance, Gillespie syndrome is more likely to be an autosomal recessive condition.

Management includes regular ophthalmologic evaluation with prescription of optical aids, physical, speech and occupational therapy for muscular re-education.

There are no reports on the natural history of the disease. Prognosis depends on the proper management and anticipation of ocular and mental symptoms and disabilities.

Expert reviewer(s)

  • Pr Francesc PALAU

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Detailed information

Article for general public
  • EN (2014)
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