Gillespie Syndrome (GLSP)

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Disease Ontology 12 DOID:0111578 OMIM 56 206700 MeSH 43 C536370 D002524 D008607 D015783 more SNOMED-CT 67 253176002 ICD10 via Orphanet 33 G11.0

UMLS via Orphanet 72 C0431401 Orphanet 58 ORPHA1065 MedGen 41 C0431401 SNOMED-CT via HPO 68 102935005 103606006 128588008 16026008 198914002 224958001 228156007 246635007 247578003 258211005 263681008 289195008 36110001 397540003 398151007 398152000 563001 56610005 60342002 69278003 77420001 7973008 85102008 91138005 95714006 more UMLS 71 C0431401

NIH Rare Diseases : ⁵² The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1065 Definition A rare, congenital , neurological disorder characterized by the association of partial bilateral aniridia with non-progressive cerebellar ataxia , and intellectual disability . Epidemiology To date, less than 30 patients have been reported in the literature. Clinical description 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, retinal hypopigmentation, and/or pigmentary macular changes leading to reduced visual acuity. 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 those showing a more complex phenotype , associating additional ocular findings and a mild dysmorphic face. Etiology 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 . One case has also been reported to be 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. Diagnostic methods A presumptive diagnosis can be made in the first months of life: on 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 occasional white matter changes, and diffuse atrophy of the cerebral hemispheres, brainstem and frontal cortex. Differential diagnosis Differential diagnosis includes Marinesco-Sjogren syndrome (see this term) in which congenital cataract is present, as well as cerebellar ataxia, intellectual disability, and aniridia (see this term). Genetic counseling Sporadic and familial cases have been observed. Although some reported families are compatible with autosomal dominant inheritance, Gillespie syndrome is more likely to be an autosomal recessive condition. Management and treatment Management includes regular ophthalmologic evaluation with prescription of optical aids, physical, speech and occupational therapy for muscular re-education. Prognosis 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. Visit the Orphanet disease page for more resources.

MalaCards based summary : Gillespie Syndrome, also known as aniridia, cerebellar ataxia, and mental retardation, is related to aniridia 1 and wilms tumor, aniridia, genitourinary anomalies, and mental retardation syndrome, and has symptoms including ataxia, cerebellar ataxia and static tremor. An important gene associated with Gillespie Syndrome is ITPR1 (Inositol 1,4,5-Trisphosphate Receptor Type 1), and among its related pathways/superpathways are Circadian entrainment and GABAergic synapse. Affiliated tissues include eye, bone and brain, and related phenotypes are intellectual disability and global developmental delay

Disease Ontology : ¹² A syndrome characterized by iris hypoplasia, congenital hypotonia, cerebellar hypoplasia, variably cognitive impairment, and ataxia that has material basis in heterozygous, homozygous, or compound heterozygous mutation in ITPR1 on chromosome 3p26.1.

Genetics Home Reference : ²⁵ Gillespie syndrome is a disorder that involves eye abnormalities, weak muscle tone from birth (congenital hypotonia), problems with balance and coordinating movements (ataxia), and mild to moderate intellectual disability. Gillespie syndrome is characterized by underdevelopment (hypoplasia) of the colored part of the eye (the iris). In most affected individuals, part of the iris is missing (partial aniridia) in both eyes. In addition, the irises have a characteristic uneven pattern known as "scalloping" at the inner (pupillary) edge. The pupils are enlarged (dilated) and are fixed, which means they do not get smaller (constrict) in response to light. These abnormalities are thought to result from problems in the development or maintenance of the tiny muscles that allow the pupil to contract (sphincter pupillae). The eye abnormalities can cause blurry vision (reduced visual acuity) and increased sensitivity to light (photophobia). Rapid, involuntary eye movements (nystagmus) can also occur in Gillespie syndrome. The balance and movement problems in Gillespie syndrome result from hypoplasia of the cerebellum, which is the part of the brain that coordinates movement. This abnormality can cause hypotonia and delayed development of motor skills such as walking. In addition, difficulty controlling the muscles of the mouth can lead to delayed speech development. The difficulties with coordination generally become noticeable in early childhood when the individual is learning these skills. People with Gillespie syndrome usually continue to have an unsteady pattern of walking (gait) and speech problems throughout life. Other features of Gillespie syndrome can include abnormalities in the bones of the spine (vertebrae) and malformations of the heart.

OMIM : ⁵⁶ Gillespie syndrome is usually diagnosed in the first year of life by the presence of fixed dilated pupils in a hypotonic infant. Affected individuals have a characteristic form of iris hypoplasia in which the pupillary border of the iris exhibits a scalloped or 'festooned' edge, with iris strands extending onto the anterior lens surface at regular intervals. The key extraocular features of Gillespie syndrome are congenital hypotonia, progressive cerebellar hypoplasia, and ataxia, as well as variable cognitive impairment that is usually mild (summary by Gerber et al., 2016 and McEntagart et al., 2016). (206700)

UniProtKB/Swiss-Prot : ⁷³ Gillespie syndrome: A rare disease characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, progressive cerebellar atrophy, and mental retardation.

Wikipedia : ⁷⁴ Gillespie syndrome, also called aniridia, cerebellar ataxia and mental deficiency. is a rare genetic... more...

Clinical features from OMIM:

206700

Search Clinical Trials , NIH Clinical Center for Gillespie Syndrome

Search GEO for disease gene expression data for Gillespie Syndrome.