MCID: WLC001
MIFTS: 42

Wolcott-Rallison Syndrome malady

Categories: Genetic diseases, Rare diseases, Bone diseases, Endocrine diseases, Fetal diseases

Aliases & Classifications for Wolcott-Rallison Syndrome

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Sources:
50OMIM, 23GeneTests, 52Orphanet, 68UniProtKB/Swiss-Prot, 12diseasecard, 48Novoseek, 66UMLS, 46NIH Rare Diseases, 38MESH via Orphanet, 29ICD10 via Orphanet, 67UMLS via Orphanet, 35MedGen, 37MeSH, 62The Human Phenotype Ontology
See all MalaCards sources

Aliases & Descriptions for Wolcott-Rallison Syndrome:

Name: Wolcott-Rallison Syndrome 50 23 52 68 12 48 66
Multiple Epiphyseal Dysplasia with Early-Onset Diabetes Mellitus 23 68
Med-Iddm Syndrome 46 68
Iddm-Med Syndrome 46 68
Wrs 52 68
 
Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus 50
Early-Onset Diabetes Mellitus with Multiple Epiphyseal Dysplasia 52
Epiphyseal Dysplasia Multiple with Early-Onset Diabetes Mellitus 46
Wolcott Rallison Syndrome 46
Romano-Ward Syndrome 66

Characteristics:

Orphanet epidemiological data:

52
wolcott-rallison syndrome:
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal

HPO:

62
wolcott-rallison syndrome:
Inheritance: autosomal recessive inheritance
Onset and clinical course: infantile onset


Classifications:



External Ids:

OMIM50 226980
Orphanet52 ORPHA1667
MESH via Orphanet38 C536739
ICD10 via Orphanet29 E13
UMLS via Orphanet67 C0432217
MedGen35 C0432217
MeSH37 D010009

Summaries for Wolcott-Rallison Syndrome

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OMIM:50 Wolcott-Rallison syndrome is a rare autosomal recessive disorder characterized by permanent neonatal or early infancy... (226980) more...

MalaCards based summary: Wolcott-Rallison Syndrome, also known as multiple epiphyseal dysplasia with early-onset diabetes mellitus, is related to long qt syndrome 1 and neonatal diabetes mellitus, and has symptoms including abnormality of the metaphyses, short stature and type ii diabetes mellitus. An important gene associated with Wolcott-Rallison Syndrome is EIF2AK3 (Eukaryotic Translation Initiation Factor 2 Alpha Kinase 3), and among its related pathways are Apoptosis Modulation and Signaling and Alzheimer's disease. Affiliated tissues include bone, pancreas and neutrophil, and related mouse phenotype endocrine/exocrine gland.

UniProtKB/Swiss-Prot:68 Wolcott-Rallison syndrome: A rare autosomal recessive disorder, characterized by permanent neonatal or early infancy insulin-dependent diabetes and, at a later age, epiphyseal dysplasia, osteoporosis, growth retardation and other multisystem manifestations, such as hepatic and renal dysfunctions, mental retardation and cardiovascular abnormalities.

Related Diseases for Wolcott-Rallison Syndrome

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Diseases related to Wolcott-Rallison Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 16)
idRelated DiseaseScoreTop Affiliating Genes
1long qt syndrome 111.0
2neonatal diabetes mellitus10.4
3hypothyroidism10.4
4acute liver failure10.3
5hepatitis10.3
6liver disease10.3
7hypoaldosteronism10.3
8spinal muscular atrophy10.0
9muscular atrophy10.0
10malaria9.9
11prostate cancer9.9
12cutaneous leishmaniasis9.9
13plasmodium vivax malaria9.9
14prostatitis9.9
15leishmaniasis9.9
16interleukin 1 receptor antagonist deficiency8.9EIF2AK3, EIF2S1, PAX4

Graphical network of diseases related to Wolcott-Rallison Syndrome:



Diseases related to wolcott-rallison syndrome

Symptoms for Wolcott-Rallison Syndrome

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Symptoms by clinical synopsis from OMIM:

226980

Clinical features from OMIM:

226980

Symptoms:

 52 (show all 62)
  • renal tubular dysfunction
  • thin vermilion border
  • epicanthus
  • triangular face
  • high forehead
  • hypermetropia
  • microdontia
  • osteopenia
  • osteoporosis
  • abnormality of the metaphyses
  • death in infancy
  • weight loss
  • dehydration
  • hyperuricemia
  • steatorrhea
  • multiple epiphyseal dysplasia
  • epiphyseal dysplasia
  • hyperglycemia
  • glycosuria
  • short stature
  • abnormality of epiphysis morphology
  • transient neonatal diabetes mellitus
  • cone-shaped epiphyses of the phalanges of the hand
  • abnormality of pancreas morphology
  • platyspondyly
  • brachydactyly syndrome
  • intellectual disability
  • muscular hypotonia
  • motor delay
  • gait disturbance
  • abnormality of cardiac morphology
  • neutropenia
  • ketoacidosis
  • hepatomegaly
  • coxa valga
  • delayed skeletal maturation
  • hip dislocation
  • genu valgum
  • narrow iliac wings
  • elevated hepatic transaminases
  • acute hepatic failure
  • intracerebral periventricular calcifications
  • short thorax
  • neurodevelopmental delay
  • enlarged thorax
  • chronic hepatic failure
  • renal insufficiency
  • nephropathy
  • microcephaly
  • hypothyroidism
  • jaundice
  • seizures
  • intrauterine growth retardation
  • exocrine pancreatic insufficiency
  • hypoglycemia
  • abnormality of neuronal migration
  • pancreatic hypoplasia
  • recurrent fractures
  • kyphosis
  • hyperlordosis
  • reduced pancreatic beta cells
  • coma

HPO human phenotypes related to Wolcott-Rallison Syndrome:

(show all 64)
id Description Frequency HPO Source Accession
1 abnormality of the metaphyses hallmark (90%) HP:0000944
2 short stature hallmark (90%) HP:0004322
3 type ii diabetes mellitus hallmark (90%) HP:0005978
4 platyspondyly typical (50%) HP:0000926
5 brachydactyly syndrome typical (50%) HP:0001156
6 gait disturbance typical (50%) HP:0001288
7 abnormality of neutrophils typical (50%) HP:0001874
8 hepatomegaly typical (50%) HP:0002240
9 delayed skeletal maturation typical (50%) HP:0002750
10 genu valgum typical (50%) HP:0002857
11 elevated hepatic transaminases typical (50%) HP:0002910
12 acute hepatic failure typical (50%) HP:0006554
13 short thorax typical (50%) HP:0010306
14 abnormality of immune system physiology typical (50%) HP:0010978
15 cognitive impairment typical (50%) HP:0100543
16 chronic hepatic failure typical (50%) HP:0100626
17 renal insufficiency occasional (7.5%) HP:0000083
18 nephropathy occasional (7.5%) HP:0000112
19 microcephaly occasional (7.5%) HP:0000252
20 hypothyroidism occasional (7.5%) HP:0000821
21 seizures occasional (7.5%) HP:0001250
22 intrauterine growth retardation occasional (7.5%) HP:0001511
23 exocrine pancreatic insufficiency occasional (7.5%) HP:0001738
24 hypoglycemia occasional (7.5%) HP:0001943
25 abnormality of neuronal migration occasional (7.5%) HP:0002269
26 recurrent fractures occasional (7.5%) HP:0002757
27 kyphosis occasional (7.5%) HP:0002808
28 hyperlordosis occasional (7.5%) HP:0003307
29 aplasia/hypoplasia of the pancreas occasional (7.5%) HP:0100800
30 renal insufficiency HP:0000083
31 high palate HP:0000218
32 microcephaly HP:0000252
33 hypertelorism HP:0000316
34 upslanted palpebral fissure HP:0000582
35 insulin-resistant diabetes mellitus HP:0000831
36 platyspondyly HP:0000926
37 osteoporosis HP:0000939
38 global developmental delay HP:0001263
39 hypertonia HP:0001276
40 carpal bone hypoplasia HP:0001498
41 barrel-shaped chest HP:0001552
42 hepatomegaly HP:0002240
43 multiple epiphyseal dysplasia HP:0002654
44 epiphyseal dysplasia HP:0002656
45 coxa valga HP:0002673
46 hip dislocation HP:0002827
47 genu valgum HP:0002857
48 narrow iliac wings HP:0002868
49 flattened epiphysis HP:0003071
50 irregular vertebral endplates HP:0003301
51 hyperlordosis HP:0003307
52 hypoplasia of the odontoid process HP:0003311
53 irregular carpal bones HP:0004236
54 short stature HP:0004322
55 preauricular pit HP:0004467
56 depressed nasal bridge HP:0005280
57 shortening of all middle phalanges of the fingers HP:0006110
58 reduced pancreatic beta cells HP:0006274
59 irregular tarsal ossification HP:0008134
60 ivory epiphyses of the toes HP:0010168
61 cone-shaped epiphyses of the phalanges of the hand HP:0010230
62 ivory epiphyses of the phalanges of the hand HP:0010234
63 small epiphyses HP:0010585
64 hip subluxation HP:0030043

UMLS symptoms related to Wolcott-Rallison Syndrome:


syncope, hepatomegaly

Drugs & Therapeutics for Wolcott-Rallison Syndrome

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Interventional clinical trials:

Search ClinicalTrials, NIH Clinical Center for Wolcott-Rallison Syndrome

Genetic Tests for Wolcott-Rallison Syndrome

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Genetic tests related to Wolcott-Rallison Syndrome:

id Genetic test Affiliating Genes
1 Multiple Epiphyseal Dysplasia with Early-Onset Diabetes Mellitus23 EIF2AK3

Anatomical Context for Wolcott-Rallison Syndrome

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MalaCards organs/tissues related to Wolcott-Rallison Syndrome:

34
Bone, Pancreas, Neutrophil, Liver, Kidney

Animal Models for Wolcott-Rallison Syndrome or affiliated genes

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MGI Mouse Phenotypes related to Wolcott-Rallison Syndrome:

39
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053798.5EIF2AK3, EIF2S1, PAX4

Publications for Wolcott-Rallison Syndrome

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Articles related to Wolcott-Rallison Syndrome:

(show all 31)
idTitleAuthorsYear
1
Os odontoideum in wolcott-rallison syndrome: a case series of 4 patients. (26860746)
2016
2
Wolcott-Rallison syndrome with novel EIF2AK3 gene mutation. (27145240)
2016
3
En bloc multiorgan transplant (liver, pancreas, and kidney) for acute liver and renal failure in a patient with wolcott-rallison syndrome. (26784269)
2016
4
RelatA+ve hypoaldosteronism in a patient with Wolcott-Rallison syndrome. (26433138)
2015
5
Liver disease and other comorbidities in Wolcott-Rallison syndrome: different phenotype and variable associations in a large cohort. (25659842)
2015
6
Liver, pancreas and kidney transplantation for the treatment of Wolcott-Rallison syndrome. (25384546)
2015
7
Anaesthesia and orphan disease: a child with Wolcott-Rallison syndrome. (25101713)
2015
8
Novel mutation in wolcott-rallison syndrome with variable expression in two omani siblings. (25960841)
2015
9
Early-onset diabetes mellitus and neurodevelopmental retardation: the first Greek case of Wolcott-Rallison syndrome. (24859506)
2014
10
Microscopic and ultrastructural features in Wolcott-Rallison syndrome, a permanent neonatal diabetes mellitus: about two autopsy cases. (25131821)
2014
11
Wolcott Rallison syndrome: a rare inherited diabetes mellitus. (24710710)
2014
12
Recurrent Hepatitis in Two Iranian Children: A Novel (Q166R) Mutation in EIF2AK3 Leading to Wolcott-Rallison Syndrome. (24032041)
2013
13
Primary hypothyroidism: an unusual manifestation of Wolcott-Rallison syndrome. (23933668)
2013
14
Frequency and spectrum of Wolcott-Rallison syndrome in Saudi Arabia: a systematic review. (23759358)
2013
15
Variable phenotype in five patients with Wolcott-Rallison syndrome due to the same EIF2AK3 (c.1259delA) mutation. (23585173)
2013
16
Primary hypothyroidism and nipple hypoplasia in a girl with Wolcott-Rallison syndrome. (24194294)
2013
17
EIF2AK3 mutations in South Indian children with permanent neonatal diabetes mellitus associated with Wolcott-Rallison syndrome. (24168455)
2013
18
Wolcott-Rallison syndrome due to a novel mutation (R491X) in EIF2AK3 gene. (22672868)
2012
19
Wolcott-Rallison syndrome. (23263430)
2012
20
A novel EIF2AK3 mutation leading to Wolcott-Rallison syndrome in a Chinese child. (21648287)
2011
21
Two novel mutations in the EIF2AK3 gene in children with Wolcott-Rallison syndrome. (21518408)
2011
22
Wolcott-Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature. (20202148)
2010
23
Wolcott-Rallison syndrome. (21050479)
2010
24
Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families. (19837917)
2009
25
Recurrent acute liver failure and mitochondriopathy in a case of Wolcott-Rallison syndrome. (18704764)
2008
26
A novel mutation in the EIF2AK3 gene with variable expressivity in two patients with Wolcott-Rallison syndrome. (16813601)
2006
27
Wolcott-Rallison syndrome: a clinical and genetic study of three children, novel mutation in EIF2AK3 and a review of the literature. (15384883)
2004
28
Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity. (15220213)
2004
29
Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene. (12086964)
2002
30
EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. (10932183)
2000
31
Organisation of the human PAX4 gene and its exclusion as a candidate for the Wolcott-Rallison syndrome. (9598721)
1998

Variations for Wolcott-Rallison Syndrome

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UniProtKB/Swiss-Prot genetic disease variations for Wolcott-Rallison Syndrome:

68
id Symbol AA change Variation ID SNP ID
1EIF2AK3p.Arg588GlnVAR_011408rs121908569

Clinvar genetic disease variations for Wolcott-Rallison Syndrome:

5
id Gene Variation Type Significance SNP ID Assembly Location
1EIF2AK3NM_004836.6(EIF2AK3): c.1192C> T (p.Gln398Ter)single nucleotide variantPathogenicrs864621972GRCh37Chr 2, 88888393: 88888393
2EIF2AK3NM_004836.6(EIF2AK3): c.1564_1565delTG (p.Trp522Glufs)deletionPathogenicrs797045558GRCh37Chr 2, 88885444: 88885445
3EIF2AK3NM_004836.6(EIF2AK3): c.1035dupT (p.Lys346Terfs)duplicationPathogenicrs869025178GRCh37Chr 2, 88890091: 88890091
4EIF2AK3NM_004836.6(EIF2AK3): c.1763G> A (p.Arg588Gln)single nucleotide variantPathogenicrs121908569GRCh37Chr 2, 88882948: 88882948
5NM_004836.6(EIF2AK3): c.2985+1G> Asingle nucleotide variantPathogenicrs869025179GRCh37Chr 2, 88870391: 88870391
6EIF2AK3EIF2AK3, 4-BP DEL, 1563GAAAdeletionPathogenic
7EIF2AK3NM_004836.6(EIF2AK3): c.994G> T (p.Glu332Ter)single nucleotide variantPathogenicrs121908570GRCh37Chr 2, 88890344: 88890344

Expression for genes affiliated with Wolcott-Rallison Syndrome

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Search GEO for disease gene expression data for Wolcott-Rallison Syndrome.

Pathways for genes affiliated with Wolcott-Rallison Syndrome

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GO Terms for genes affiliated with Wolcott-Rallison Syndrome

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Biological processes related to Wolcott-Rallison Syndrome according to GeneCards Suite gene sharing:

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1response to manganese-induced endoplasmic reticulum stressGO:19907379.8EIF2AK3, EIF2S1
2negative regulation of translational initiation in response to stressGO:00320579.8EIF2AK3, EIF2S1
3PERK-mediated unfolded protein responseGO:00364999.5EIF2AK3, EIF2S1
4cellular response to amino acid starvationGO:00341989.4EIF2AK3, EIF2S1
5endocrine pancreas developmentGO:00310189.4EIF2AK3, PAX4
6response to endoplasmic reticulum stressGO:00349769.3EIF2AK3, EIF2S1
7protein autophosphorylationGO:00467779.2EIF2AK3, EIF2S1

Sources for Wolcott-Rallison Syndrome

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
25GTR
26HGMD
27HMDB
28ICD10
29ICD10 via Orphanet
30ICD9CM
31IUPHAR
32KEGG
35MedGen
37MeSH
38MESH via Orphanet
39MGI
42NCI
43NCIt
44NDF-RT
47NINDS
48Novoseek
50OMIM
51OMIM via Orphanet
55PubMed
56QIAGEN
61SNOMED-CT via Orphanet
65Tumor Gene Family of Databases
66UMLS
67UMLS via Orphanet