MCID: GLL028
MIFTS: 33

Gillespie Syndrome

Categories: Genetic diseases, Rare diseases, Mental diseases, Neuronal diseases, Eye diseases, Fetal diseases

Aliases & Classifications for Gillespie Syndrome

MalaCards integrated aliases for Gillespie Syndrome:

Name: Gillespie Syndrome 53 72 49 24 55 71 28 13 69
Aniridia, Cerebellar Ataxia, and Mental Retardation 53 24 71
Aniridia, Cerebellar Ataxia and Mental Deficiency 49 71
Glsp 53 71
Aniridia-Cerebellar Ataxia-Intellectual Disability Syndrome 55
Aniridia-Cerebellar Ataxia-Intellectual Disability 24
Partial Aniridia-Cerebellar Ataxia-Oligophrenia 24
Aniridia-Cerebellar Ataxia-Mental Deficiency 24

Characteristics:

Orphanet epidemiological data:

55
aniridia-cerebellar ataxia-intellectual disability syndrome
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal dominant
autosomal recessive (in some patients)

Miscellaneous:
three patients with homozygous or compound heterozygous mutations have been reported (last curated june 2016)


HPO:

31
gillespie syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Gillespie Syndrome

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1065Disease definitionAniridia-cerebellar ataxia-intellectual disabilitysyndrome, also known as Gillespie syndrome, is a rare, congenital, neurological disorder characterized by the association of partial bilateral aniridia with non-progressive cerebellar ataxia, and intellectual disability.EpidemiologyTo date, less than 30 patients have been reported in the literature.Clinical descriptionAniridia 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.EtiologyThe 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 methodsA 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 diagnosisDifferential diagnosis includes Marinesco-Sjögren syndrome (see this term) in which congenital cataract is present, as well as cerebellar ataxia, intellectual disability, and aniridia (see this term).Genetic counselingSporadic 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 treatmentManagement includes regular ophthalmologic evaluation with prescription of optical aids, physical, speech and occupational therapy for muscular re-education.PrognosisThere 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. Last updated: 12/1/2014

MalaCards based summary : Gillespie Syndrome, also known as aniridia, cerebellar ataxia, and mental retardation, is related to aniridia 1 and aniridia and absent patella, and has symptoms including ataxia, scanning speech and intellectual disability. An important gene associated with Gillespie Syndrome is ITPR1 (Inositol 1,4,5-Trisphosphate Receptor Type 1), and among its related pathways/superpathways is Transcriptional Regulatory Network in Embryonic Stem Cell. Affiliated tissues include eye.

OMIM : 53 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 : 71 Gillespie syndrome: A rare disease characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, progressive cerebellar atrophy, and mental retardation.

Genetics Home Reference : 24 Gillespie syndrome is a disorder that involves eye abnormalities, problems with balance and coordinating movements (ataxia), and mild to moderate intellectual disability.

Related Diseases for Gillespie Syndrome

Diseases related to Gillespie Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 aniridia 1 11.3
2 aniridia and absent patella 10.9
3 aniridia 2 10.9
4 ataxia and polyneuropathy, adult-onset 10.2
5 aceruloplasminemia 10.2
6 ataxia-oculomotor apraxia 3 10.2
7 esophagitis 9.9

Graphical network of the top 20 diseases related to Gillespie Syndrome:



Diseases related to Gillespie Syndrome

Symptoms & Phenotypes for Gillespie Syndrome

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
ataxia
slurred speech
postural tremor
delayed motor development
mental retardation, mild to severe
more
Head And Neck Eyes:
nystagmus
iris hypoplasia
scalloped pupillary margins of iris
visual impairment, mild to moderate


Clinical features from OMIM:

206700

Human phenotypes related to Gillespie Syndrome:

55 31 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001251
2 scanning speech 55 31 frequent (33%) Frequent (79-30%) HP:0002168
3 intellectual disability 55 31 hallmark (90%) Very frequent (99-80%) HP:0001249
4 muscular hypotonia 55 31 frequent (33%) Frequent (79-30%) HP:0001252
5 global developmental delay 55 31 hallmark (90%) Very frequent (99-80%) HP:0001263
6 abnormality of movement 55 31 frequent (33%) Frequent (79-30%) HP:0100022
7 hearing abnormality 55 31 occasional (7.5%) Occasional (29-5%) HP:0000364
8 mask-like facies 55 31 hallmark (90%) Very frequent (99-80%) HP:0000298
9 abnormality of the pulmonary artery 55 31 occasional (7.5%) Occasional (29-5%) HP:0004414
10 aniridia 55 31 hallmark (90%) Very frequent (99-80%) HP:0000526
11 nystagmus 31 HP:0000639
12 neurological speech impairment 55 Frequent (79-30%)
13 visual impairment 31 HP:0000505
14 slurred speech 31 HP:0001350
15 cerebellar hypoplasia 31 HP:0001321
16 hypoplasia of the iris 31 HP:0007676
17 postural tremor 31 HP:0002174
18 motor delay 31 HP:0001270

UMLS symptoms related to Gillespie Syndrome:


static tremor, cerebellar ataxia, ataxia

Drugs & Therapeutics for Gillespie Syndrome

Search Clinical Trials , NIH Clinical Center for Gillespie Syndrome

Genetic Tests for Gillespie Syndrome

Genetic tests related to Gillespie Syndrome:

# Genetic test Affiliating Genes
1 Gillespie Syndrome 28 ITPR1 PAX6

Anatomical Context for Gillespie Syndrome

MalaCards organs/tissues related to Gillespie Syndrome:

38
Eye

Publications for Gillespie Syndrome

Articles related to Gillespie Syndrome:

(show all 20)
# Title Authors Year
1
Additional features of Gillespie syndrome in two Brazilian siblings with a novel ITPR1 homozygous pathogenic variant. ( 29169895 )
2018
2
Identification of novel and hotspot mutations in the channel domain of ITPR1 in two patients with Gillespie syndrome. ( 28698159 )
2017
3
A Restricted Repertoire of De Novo Mutations in ITPR1 Cause Gillespie Syndrome with Evidence for Dominant-Negative Effect. ( 27108798 )
2016
4
Genetic Analysis of 'PAX6-Negative' Individuals with Aniridia or Gillespie Syndrome. ( 27124303 )
2016
5
Recessive and Dominant De Novo ITPR1 Mutations Cause Gillespie Syndrome. ( 27108797 )
2016
6
The Triad of Non-progressive Cerebellar Ataxia, Partial Aniridia and Psychomotor Delay - Gillespie Syndrome. ( 27109391 )
2016
7
Esophageal dysmotility in gillespie syndrome. ( 24199016 )
2013
8
Gillespie syndrome with impaired accommodation. ( 19213284 )
2009
9
Gillespie syndrome with impaired accommodation. ( 19791732 )
2009
10
Cerebellar cognitive affective syndrome without global mental retardation in two relatives with Gillespie syndrome. ( 18387531 )
2008
11
Gillespie syndrome: additional findings and parental consanguinity. ( 17558851 )
2007
12
Gillespie syndrome: two further cases. ( 16900933 )
2006
13
[Present limitations of molecular biological diagnostics in Gillespie syndrome]. ( 11305191 )
2001
14
Gillespie syndrome phenotype with a t(X;11)(p22.32;p12) de novo translocation. ( 9512164 )
1998
15
Gillespie syndrome: a report of two further cases. ( 9217210 )
1997
16
Absence of PAX6 gene mutations in Gillespie syndrome (partial aniridia, cerebellar ataxia, and mental retardation). ( 8188215 )
1994
17
Gillespie syndrome, partial aniridia, cerebellar ataxia and mental retardation in mother and daughter. ( 7952360 )
1993
18
Gillespie syndrome reported as bilateral congenital mydriasis. ( 7509186 )
1993
19
Syndrome of partial aniridia, cerebellar ataxia, and mental retardation--Gillespie syndrome. ( 2333873 )
1990
20
Partial aniridia, cerebellar ataxia, and mental deficiency (Gillespie syndrome) in two brothers. ( 3189393 )
1988

Variations for Gillespie Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Gillespie Syndrome:

71
# Symbol AA change Variation ID SNP ID
1 ITPR1 p.Glu2109Gln VAR_077462
2 ITPR1 p.Gly2554Arg VAR_077463 rs752281590
3 ITPR1 p.Phe2601Leu VAR_077464 rs878853176

ClinVar genetic disease variations for Gillespie Syndrome:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 ITPR1 NM_001168272.1(ITPR1): c.4654C> T (p.Gln1552Ter) single nucleotide variant Pathogenic rs878853171 GRCh37 Chromosome 3, 4747892: 4747892
2 ITPR1 NM_001168272.1(ITPR1): c.2137C> T (p.Arg713Ter) single nucleotide variant Pathogenic rs878853172 GRCh37 Chromosome 3, 4712588: 4712588
3 ITPR1 NM_001168272.1(ITPR1): c.6465+3A> T single nucleotide variant Pathogenic rs878853173 GRCh37 Chromosome 3, 4824428: 4824428
4 ITPR1 NM_001168272.1(ITPR1): c.6763+5G> T single nucleotide variant Pathogenic rs878853174 GRCh37 Chromosome 3, 4829828: 4829828
5 ITPR1 NM_001168272.1(ITPR1): c.7786_7788delAAG (p.Lys2596del) deletion Pathogenic rs878853175 GRCh37 Chromosome 3, 4856866: 4856868
6 ITPR1 NM_001168272.1(ITPR1): c.7758T> G (p.Phe2586Leu) single nucleotide variant Pathogenic rs878853176 GRCh37 Chromosome 3, 4856838: 4856838
7 ITPR1 NM_001168272.1(ITPR1): c.6281A> G (p.Glu2094Gly) single nucleotide variant Pathogenic rs878853177 GRCh37 Chromosome 3, 4821268: 4821268
8 ITPR1 NM_001168272.1(ITPR1): c.7615G> A (p.Gly2539Arg) single nucleotide variant Pathogenic rs752281590 GRCh37 Chromosome 3, 4856205: 4856205
9 ITPR1 NM_001168272.1(ITPR1): c.7615G> C (p.Gly2539Arg) single nucleotide variant Pathogenic rs752281590 GRCh37 Chromosome 3, 4856205: 4856205
10 ITPR1 NM_001099952.2(ITPR1): c.2952_2953insTATA (p.Val985Tyrfs) insertion Pathogenic GRCh38 Chromosome 3, 4680564: 4680565

Expression for Gillespie Syndrome

Search GEO for disease gene expression data for Gillespie Syndrome.

Pathways for Gillespie Syndrome

Pathways related to Gillespie Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.25 ITPR1 PAX6

GO Terms for Gillespie Syndrome

Sources for Gillespie Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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