MCID: GLL028
MIFTS: 33

Gillespie Syndrome

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

Aliases & Classifications for Gillespie Syndrome

MalaCards integrated aliases for Gillespie Syndrome:

Name: Gillespie Syndrome 57 76 53 25 59 75 29 13 6 73
Aniridia, Cerebellar Ataxia, and Mental Retardation 57 25 75 40
Aniridia, Cerebellar Ataxia and Mental Deficiency 53 75
Glsp 57 75
Aniridia-Cerebellar Ataxia-Intellectual Disability Syndrome 59
Aniridia, Cerebellar Ataxia, and Intellectual Disability 6
Aniridia-Cerebellar Ataxia-Intellectual Disability 25
Partial Aniridia-Cerebellar Ataxia-Oligophrenia 25
Aniridia-Cerebellar Ataxia-Mental Deficiency 25

Characteristics:

Orphanet epidemiological data:

59
aniridia-cerebellar ataxia-intellectual disability syndrome
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
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:

32
gillespie syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Gillespie Syndrome

NIH Rare Diseases : 53 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.

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, 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 is fMLP Pathway. Affiliated tissues include eye, and related phenotypes are mask-like facies and hearing abnormality

OMIM : 57 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 : 75 Gillespie syndrome: A rare disease characterized by bilateral iris hypoplasia, congenital hypotonia, non-progressive ataxia, progressive cerebellar atrophy, and mental retardation.

Genetics Home Reference : 25 Gillespie syndrome is a disorder that involves eye abnormalities, problems with balance and coordinating movements (ataxia), and mild to moderate intellectual disability.

Wikipedia : 76 Gillespie syndrome, also called aniridia, cerebellar ataxia and mental deficiency. is a rare genetic... more...

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 10.9
2 aniridia and absent patella 10.9
3 aniridia 2 10.9
4 aceruloplasminemia 10.2
5 ataxia-oculomotor apraxia 3 10.2
6 esophagitis 9.9
7 trehalase deficiency 9.0 ITPR1 PAX6

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:

57
Head And Neck Eyes:
nystagmus
iris hypoplasia
scalloped pupillary margins of iris
visual impairment, mild to moderate

Neurologic Central Nervous System:
ataxia
slurred speech
postural tremor
delayed motor development
mental retardation, mild to severe
more

Clinical features from OMIM:

206700

Human phenotypes related to Gillespie Syndrome:

59 32 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 mask-like facies 59 32 hallmark (90%) Very frequent (99-80%) HP:0000298
2 hearing abnormality 59 32 occasional (7.5%) Occasional (29-5%) HP:0000364
3 aniridia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000526
4 intellectual disability 59 32 hallmark (90%) Very frequent (99-80%) HP:0001249
5 ataxia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001251
6 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
7 global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0001263
8 scanning speech 59 32 frequent (33%) Frequent (79-30%) HP:0002168
9 abnormality of the pulmonary artery 59 32 occasional (7.5%) Occasional (29-5%) HP:0004414
10 abnormality of movement 59 32 frequent (33%) Frequent (79-30%) HP:0100022
11 neurological speech impairment 59 Frequent (79-30%)
12 visual impairment 32 HP:0000505
13 nystagmus 32 HP:0000639
14 motor delay 32 HP:0001270
15 cerebellar hypoplasia 32 HP:0001321
16 slurred speech 32 HP:0001350
17 postural tremor 32 HP:0002174
18 hypoplasia of the iris 32 HP:0007676

UMLS symptoms related to Gillespie Syndrome:


ataxia, cerebellar ataxia, static tremor

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 29 ITPR1 PAX6

Anatomical Context for Gillespie Syndrome

MalaCards organs/tissues related to Gillespie Syndrome:

41
Eye

Publications for Gillespie Syndrome

Articles related to Gillespie Syndrome:

(show all 21)
# Title Authors Year
1
A novel splice site variant in ITPR1 gene underlying recessive Gillespie syndrome. ( 29663667 )
2018
2
Additional features of Gillespie syndrome in two Brazilian siblings with a novel ITPR1 homozygous pathogenic variant. ( 29169895 )
2018
3
Identification of novel and hotspot mutations in the channel domain of ITPR1 in two patients with Gillespie syndrome. ( 28698159 )
2017
4
Genetic Analysis of 'PAX6-Negative' Individuals with Aniridia or Gillespie Syndrome. ( 27124303 )
2016
5
The Triad of Non-progressive Cerebellar Ataxia, Partial Aniridia and Psychomotor Delay - Gillespie Syndrome. ( 27109391 )
2016
6
Recessive and Dominant De Novo ITPR1 Mutations Cause Gillespie Syndrome. ( 27108797 )
2016
7
A Restricted Repertoire of De Novo Mutations in ITPR1 Cause Gillespie Syndrome with Evidence for Dominant-Negative Effect. ( 27108798 )
2016
8
Esophageal dysmotility in gillespie syndrome. ( 24199016 )
2013
9
Gillespie syndrome with impaired accommodation. ( 19791732 )
2009
10
Gillespie syndrome with impaired accommodation. ( 19213284 )
2009
11
Cerebellar cognitive affective syndrome without global mental retardation in two relatives with Gillespie syndrome. ( 18387531 )
2008
12
Gillespie syndrome: additional findings and parental consanguinity. ( 17558851 )
2007
13
Gillespie syndrome: two further cases. ( 16900933 )
2006
14
[Present limitations of molecular biological diagnostics in Gillespie syndrome]. ( 11305191 )
2001
15
Gillespie syndrome phenotype with a t(X;11)(p22.32;p12) de novo translocation. ( 9512164 )
1998
16
Gillespie syndrome: a report of two further cases. ( 9217210 )
1997
17
Absence of PAX6 gene mutations in Gillespie syndrome (partial aniridia, cerebellar ataxia, and mental retardation). ( 8188215 )
1994
18
Gillespie syndrome reported as bilateral congenital mydriasis. ( 7509186 )
1993
19
Gillespie syndrome, partial aniridia, cerebellar ataxia and mental retardation in mother and daughter. ( 7952360 )
1993
20
Syndrome of partial aniridia, cerebellar ataxia, and mental retardation--Gillespie syndrome. ( 2333873 )
1990
21
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:

75
# 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
(show top 50) (show all 192)
# Gene Variation Type Significance SNP ID Assembly Location
1 PAX6 NM_000280.4(PAX6): c.-129+9G> A single nucleotide variant Benign/Likely benign rs56139994 GRCh38 Chromosome 11, 31810819: 31810819
2 PAX6 NM_000280.4(PAX6): c.-129+9G> A single nucleotide variant Benign/Likely benign rs56139994 GRCh37 Chromosome 11, 31832367: 31832367
3 ITPR1 NM_001168272.1(ITPR1): c.4654C> T (p.Gln1552Ter) single nucleotide variant Pathogenic rs878853171 GRCh37 Chromosome 3, 4747892: 4747892
4 ITPR1 NM_001168272.1(ITPR1): c.4654C> T (p.Gln1552Ter) single nucleotide variant Pathogenic rs878853171 GRCh38 Chromosome 3, 4706208: 4706208
5 ITPR1 NM_001168272.1(ITPR1): c.2137C> T (p.Arg713Ter) single nucleotide variant Pathogenic rs878853172 GRCh37 Chromosome 3, 4712588: 4712588
6 ITPR1 NM_001168272.1(ITPR1): c.2137C> T (p.Arg713Ter) single nucleotide variant Pathogenic rs878853172 GRCh38 Chromosome 3, 4670904: 4670904
7 ITPR1 NM_001168272.1(ITPR1): c.6465+3A> T single nucleotide variant Pathogenic rs878853173 GRCh37 Chromosome 3, 4824428: 4824428
8 ITPR1 NM_001168272.1(ITPR1): c.6465+3A> T single nucleotide variant Pathogenic rs878853173 GRCh38 Chromosome 3, 4782744: 4782744
9 ITPR1 NM_001168272.1(ITPR1): c.6763+5G> T single nucleotide variant Pathogenic rs878853174 GRCh37 Chromosome 3, 4829828: 4829828
10 ITPR1 NM_001168272.1(ITPR1): c.6763+5G> T single nucleotide variant Pathogenic rs878853174 GRCh38 Chromosome 3, 4788144: 4788144
11 ITPR1 NM_001168272.1(ITPR1): c.7786_7788delAAG (p.Lys2596del) deletion Pathogenic rs878853175 GRCh37 Chromosome 3, 4856866: 4856868
12 ITPR1 NM_001168272.1(ITPR1): c.7786_7788delAAG (p.Lys2596del) deletion Pathogenic rs878853175 GRCh38 Chromosome 3, 4815182: 4815184
13 ITPR1 NM_001168272.1(ITPR1): c.7758T> G (p.Phe2586Leu) single nucleotide variant Pathogenic rs878853176 GRCh37 Chromosome 3, 4856838: 4856838
14 ITPR1 NM_001168272.1(ITPR1): c.7758T> G (p.Phe2586Leu) single nucleotide variant Pathogenic rs878853176 GRCh38 Chromosome 3, 4815154: 4815154
15 ITPR1 NM_001168272.1(ITPR1): c.6281A> G (p.Glu2094Gly) single nucleotide variant Pathogenic rs878853177 GRCh37 Chromosome 3, 4821268: 4821268
16 ITPR1 NM_001168272.1(ITPR1): c.6281A> G (p.Glu2094Gly) single nucleotide variant Pathogenic rs878853177 GRCh38 Chromosome 3, 4779584: 4779584
17 ITPR1 NM_002222.5(ITPR1): c.7471G> A (p.Gly2491Arg) single nucleotide variant Pathogenic rs752281590 GRCh37 Chromosome 3, 4856205: 4856205
18 ITPR1 NM_002222.5(ITPR1): c.7471G> A (p.Gly2491Arg) single nucleotide variant Pathogenic rs752281590 GRCh38 Chromosome 3, 4814521: 4814521
19 ITPR1 NM_001168272.1(ITPR1): c.7615G> C (p.Gly2539Arg) single nucleotide variant Pathogenic rs752281590 GRCh38 Chromosome 3, 4814521: 4814521
20 ITPR1 NM_001168272.1(ITPR1): c.7615G> C (p.Gly2539Arg) single nucleotide variant Pathogenic rs752281590 GRCh37 Chromosome 3, 4856205: 4856205
21 PAX6 NM_001604.5(PAX6): c.808-12C> T single nucleotide variant Benign rs667773 GRCh37 Chromosome 11, 31815362: 31815362
22 PAX6 NM_001604.5(PAX6): c.808-12C> T single nucleotide variant Benign rs667773 GRCh38 Chromosome 11, 31793814: 31793814
23 PAX6 NM_000280.4(PAX6): c.1137A> C (p.Thr379=) single nucleotide variant Conflicting interpretations of pathogenicity rs143477661 GRCh37 Chromosome 11, 31812304: 31812304
24 PAX6 NM_000280.4(PAX6): c.1137A> C (p.Thr379=) single nucleotide variant Conflicting interpretations of pathogenicity rs143477661 GRCh38 Chromosome 11, 31790756: 31790756
25 PAX6 NM_000280.4(PAX6): c.*4627A> C single nucleotide variant Likely benign rs140971065 GRCh37 Chromosome 11, 31806855: 31806855
26 PAX6 NM_000280.4(PAX6): c.*4627A> C single nucleotide variant Likely benign rs140971065 GRCh38 Chromosome 11, 31785307: 31785307
27 PAX6 NM_000280.4(PAX6): c.*4076A> C single nucleotide variant Uncertain significance rs886048183 GRCh37 Chromosome 11, 31807406: 31807406
28 PAX6 NM_000280.4(PAX6): c.*4076A> C single nucleotide variant Uncertain significance rs886048183 GRCh38 Chromosome 11, 31785858: 31785858
29 PAX6 NM_000280.4(PAX6): c.*4003G> T single nucleotide variant Uncertain significance rs886048184 GRCh38 Chromosome 11, 31785931: 31785931
30 PAX6 NM_000280.4(PAX6): c.*4003G> T single nucleotide variant Uncertain significance rs886048184 GRCh37 Chromosome 11, 31807479: 31807479
31 PAX6 NM_000280.4(PAX6): c.*3318A> G single nucleotide variant Likely benign rs371438311 GRCh37 Chromosome 11, 31808164: 31808164
32 PAX6 NM_000280.4(PAX6): c.*3318A> G single nucleotide variant Likely benign rs371438311 GRCh38 Chromosome 11, 31786616: 31786616
33 PAX6 NM_000280.4(PAX6): c.*2901T> C single nucleotide variant Likely benign rs542906080 GRCh37 Chromosome 11, 31808581: 31808581
34 PAX6 NM_000280.4(PAX6): c.*2901T> C single nucleotide variant Likely benign rs542906080 GRCh38 Chromosome 11, 31787033: 31787033
35 PAX6 NM_000280.4(PAX6): c.*2705_*2707delAGC deletion Uncertain significance rs886048189 GRCh37 Chromosome 11, 31808775: 31808777
36 PAX6 NM_000280.4(PAX6): c.*2705_*2707delAGC deletion Uncertain significance rs886048189 GRCh38 Chromosome 11, 31787227: 31787229
37 PAX6 NM_000280.4(PAX6): c.*1521C> T single nucleotide variant Uncertain significance rs886048196 GRCh37 Chromosome 11, 31809961: 31809961
38 PAX6 NM_000280.4(PAX6): c.*1521C> T single nucleotide variant Uncertain significance rs886048196 GRCh38 Chromosome 11, 31788413: 31788413
39 PAX6 NM_000280.4(PAX6): c.*1394A> C single nucleotide variant Uncertain significance rs776894983 GRCh37 Chromosome 11, 31810088: 31810088
40 PAX6 NM_000280.4(PAX6): c.*1394A> C single nucleotide variant Uncertain significance rs776894983 GRCh38 Chromosome 11, 31788540: 31788540
41 PAX6 NM_000280.4(PAX6): c.*1287A> T single nucleotide variant Likely benign rs576321279 GRCh37 Chromosome 11, 31810195: 31810195
42 PAX6 NM_000280.4(PAX6): c.*1287A> T single nucleotide variant Likely benign rs576321279 GRCh38 Chromosome 11, 31788647: 31788647
43 PAX6 NM_000280.4(PAX6): c.*1184A> T single nucleotide variant Benign rs1506 GRCh37 Chromosome 11, 31810298: 31810298
44 PAX6 NM_000280.4(PAX6): c.*1184A> T single nucleotide variant Benign rs1506 GRCh38 Chromosome 11, 31788750: 31788750
45 PAX6 NM_000280.4(PAX6): c.*1063A> G single nucleotide variant Benign rs117590302 GRCh37 Chromosome 11, 31810419: 31810419
46 PAX6 NM_000280.4(PAX6): c.*1063A> G single nucleotide variant Benign rs117590302 GRCh38 Chromosome 11, 31788871: 31788871
47 PAX6 NM_000280.4(PAX6): c.327G> A (p.Glu109=) single nucleotide variant Benign/Likely benign rs114384476 GRCh37 Chromosome 11, 31823139: 31823139
48 PAX6 NM_000280.4(PAX6): c.327G> A (p.Glu109=) single nucleotide variant Benign/Likely benign rs114384476 GRCh38 Chromosome 11, 31801591: 31801591
49 PAX6 NM_000280.4(PAX6): c.142-8C> T single nucleotide variant Uncertain significance rs886048203 GRCh37 Chromosome 11, 31823332: 31823332
50 PAX6 NM_000280.4(PAX6): c.142-8C> T single nucleotide variant Uncertain significance rs886048203 GRCh38 Chromosome 11, 31801784: 31801784

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
Show member pathways
11.47 ITPR1 PAX6

GO Terms for Gillespie Syndrome

Sources for Gillespie Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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