MCID: WLC001
MIFTS: 40

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:
12diseasecard, 24GeneTests, 31ICD10 via Orphanet, 37MedGen, 39MeSH, 40MESH via Orphanet, 48NIH Rare Diseases, 50Novoseek, 52OMIM, 54Orphanet, 64The Human Phenotype Ontology, 68UMLS, 69UMLS via Orphanet, 70UniProtKB/Swiss-Prot
See all MalaCards sources

Aliases & Descriptions for Wolcott-Rallison Syndrome:

Name: Wolcott-Rallison Syndrome 52 24 54 70 12 50 68
Multiple Epiphyseal Dysplasia with Early-Onset Diabetes Mellitus 24 70
Iddm-Med Syndrome 48 70
Med-Iddm Syndrome 48 70
Wrs 54 70
 
Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus 52
Early-Onset Diabetes Mellitus with Multiple Epiphyseal Dysplasia 54
Epiphyseal Dysplasia Multiple with Early-Onset Diabetes Mellitus 48
Wolcott Rallison Syndrome 48
Romano-Ward Syndrome 68

Characteristics:

Orphanet epidemiological data:

54
wolcott-rallison syndrome:
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal

HPO:

64
wolcott-rallison syndrome:
Inheritance: autosomal recessive inheritance
Onset and clinical course: infantile onset

Classifications:



External Ids:

OMIM52 226980
Orphanet54 ORPHA1667
MESH via Orphanet40 C536739
UMLS via Orphanet69 C0432217
ICD10 via Orphanet31 E13
MedGen37 C0432217
MeSH39 D010009

Summaries for Wolcott-Rallison Syndrome

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OMIM:52 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 Unfolded Protein Response (UPR) and Apoptosis Modulation and Signaling. Affiliated tissues include bone, pancreas and liver.

UniProtKB/Swiss-Prot:70 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 110.8
2neonatal diabetes mellitus10.3
3hypothyroidism10.3
4acute liver failure10.1
5hepatitis10.1
6liver disease10.1
7hypoaldosteronism10.1
8spinal muscular atrophy9.9
9muscular atrophy9.9
10malaria9.7
11prostate cancer9.7
12cutaneous leishmaniasis9.7
13plasmodium vivax malaria9.7
14prostatitis9.7
15leishmaniasis9.7
16interleukin 1 receptor antagonist deficiency9.3EIF2AK3, EIF2S1, PAX4

Graphical network of diseases related to Wolcott-Rallison Syndrome:



Diseases related to wolcott-rallison syndrome

Symptoms & Phenotypes for Wolcott-Rallison Syndrome

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Symptoms by clinical synopsis from OMIM:

226980

Clinical features from OMIM:

226980

Human phenotypes related to Wolcott-Rallison Syndrome:

 64 54 (show all 87)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of the metaphyses64 54 hallmark (90%) Very frequent (99-80%) HP:0000944
2 short stature64 54 hallmark (90%) Very frequent (99-80%) HP:0004322
3 type ii diabetes mellitus64 hallmark (90%) HP:0005978
4 platyspondyly64 54 typical (50%) Frequent (79-30%) HP:0000926
5 brachydactyly syndrome64 54 typical (50%) Frequent (79-30%) HP:0001156
6 gait disturbance64 54 typical (50%) Frequent (79-30%) HP:0001288
7 abnormality of neutrophils64 typical (50%) HP:0001874
8 hepatomegaly64 54 typical (50%) Frequent (79-30%) HP:0002240
9 delayed skeletal maturation64 54 typical (50%) Frequent (79-30%) HP:0002750
10 genu valgum64 54 typical (50%) Frequent (79-30%) HP:0002857
11 elevated hepatic transaminases64 54 typical (50%) Frequent (79-30%) HP:0002910
12 acute hepatic failure64 54 typical (50%) Frequent (79-30%) HP:0006554
13 short thorax64 54 typical (50%) Frequent (79-30%) HP:0010306
14 abnormality of immune system physiology64 typical (50%) HP:0010978
15 cognitive impairment64 typical (50%) HP:0100543
16 chronic hepatic failure64 54 typical (50%) Frequent (79-30%) HP:0100626
17 renal insufficiency64 54 occasional (7.5%) Occasional (29-5%) HP:0000083
18 nephropathy64 54 occasional (7.5%) Occasional (29-5%) HP:0000112
19 microcephaly64 54 occasional (7.5%) Occasional (29-5%) HP:0000252
20 hypothyroidism64 54 occasional (7.5%) Occasional (29-5%) HP:0000821
21 seizures64 54 occasional (7.5%) Occasional (29-5%) HP:0001250
22 intrauterine growth retardation64 54 occasional (7.5%) Occasional (29-5%) HP:0001511
23 exocrine pancreatic insufficiency64 54 occasional (7.5%) Occasional (29-5%) HP:0001738
24 hypoglycemia64 54 occasional (7.5%) Occasional (29-5%) HP:0001943
25 abnormality of neuronal migration64 54 occasional (7.5%) Occasional (29-5%) HP:0002269
26 recurrent fractures64 54 occasional (7.5%) Occasional (29-5%) HP:0002757
27 kyphosis64 54 occasional (7.5%) Occasional (29-5%) HP:0002808
28 hyperlordosis64 54 occasional (7.5%) Occasional (29-5%) HP:0003307
29 aplasia/hypoplasia of the pancreas64 occasional (7.5%) HP:0100800
30 high palate64 HP:0000218
31 hypertelorism64 HP:0000316
32 upslanted palpebral fissure64 HP:0000582
33 insulin-resistant diabetes mellitus64 HP:0000831
34 osteoporosis64 54 Very frequent (99-80%) HP:0000939
35 global developmental delay64 HP:0001263
36 hypertonia64 HP:0001276
37 carpal bone hypoplasia64 HP:0001498
38 barrel-shaped chest64 HP:0001552
39 multiple epiphyseal dysplasia64 54 Very frequent (99-80%) HP:0002654
40 epiphyseal dysplasia64 54 Very frequent (99-80%) HP:0002656
41 coxa valga64 54 Frequent (79-30%) HP:0002673
42 hip dislocation64 54 Frequent (79-30%) HP:0002827
43 narrow iliac wings64 54 Frequent (79-30%) HP:0002868
44 flattened epiphysis64 HP:0003071
45 irregular vertebral endplates64 HP:0003301
46 hypoplasia of the odontoid process64 HP:0003311
47 irregular carpal bones64 HP:0004236
48 preauricular pit64 HP:0004467
49 depressed nasal bridge64 HP:0005280
50 shortening of all middle phalanges of the fingers64 HP:0006110
51 reduced pancreatic beta cells64 54 Occasional (29-5%) HP:0006274
52 irregular tarsal ossification64 HP:0008134
53 ivory epiphyses of the toes64 HP:0010168
54 cone-shaped epiphyses of the phalanges of the hand64 54 Very frequent (99-80%) HP:0010230
55 ivory epiphyses of the phalanges of the hand64 HP:0010234
56 small epiphyses64 HP:0010585
57 hip subluxation64 HP:0030043
58 renal tubular dysfunction54 Very frequent (99-80%)
59 thin vermilion border54 Very frequent (99-80%)
60 epicanthus54 Very frequent (99-80%)
61 triangular face54 Very frequent (99-80%)
62 high forehead54 Very frequent (99-80%)
63 hypermetropia54 Very frequent (99-80%)
64 microdontia54 Very frequent (99-80%)
65 osteopenia54 Very frequent (99-80%)
66 death in infancy54 Very frequent (99-80%)
67 weight loss54 Very frequent (99-80%)
68 dehydration54 Very frequent (99-80%)
69 hyperuricemia54 Very frequent (99-80%)
70 steatorrhea54 Very frequent (99-80%)
71 hyperglycemia54 Very frequent (99-80%)
72 glycosuria54 Very frequent (99-80%)
73 abnormality of epiphysis morphology54 Very frequent (99-80%)
74 transient neonatal diabetes mellitus54 Very frequent (99-80%)
75 abnormality of pancreas morphology54 Very frequent (99-80%)
76 intellectual disability54 Frequent (79-30%)
77 muscular hypotonia54 Frequent (79-30%)
78 motor delay54 Frequent (79-30%)
79 abnormal heart morphology54 Frequent (79-30%)
80 neutropenia54 Frequent (79-30%)
81 ketoacidosis54 Frequent (79-30%)
82 intracerebral periventricular calcifications54 Frequent (79-30%)
83 neurodevelopmental delay54 Frequent (79-30%)
84 enlarged thorax54 Frequent (79-30%)
85 jaundice54 Occasional (29-5%)
86 pancreatic hypoplasia54 Occasional (29-5%)
87 coma54 Very rare (<4-1%)

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 Mellitus24 EIF2AK3

Anatomical Context for Wolcott-Rallison Syndrome

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MalaCards organs/tissues related to Wolcott-Rallison Syndrome:

36
Bone, Pancreas, Liver, Neutrophil, Heart, Kidney

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:

70
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
1KCNE1NM_000219.5(KCNE1): c.253G> A (p.Asp85Asn)SNVLikely pathogenic, Pathogenic, risk factorrs1805128GRCh37Chr 21, 35821680: 35821680
2EIF2AK3NM_004836.6(EIF2AK3): c.1192C> T (p.Gln398Ter)SNVPathogenicrs864621972GRCh37Chr 2, 88888393: 88888393
3EIF2AK3NM_004836.6(EIF2AK3): c.1564_1565delTG (p.Trp522Glufs)deletionPathogenicrs797045558GRCh38Chr 2, 88585926: 88585927
4EIF2AK3NM_004836.6(EIF2AK3): c.1035dupT (p.Lys346Terfs)duplicationPathogenicrs869025178GRCh37Chr 2, 88890091: 88890091
5EIF2AK3NM_004836.6(EIF2AK3): c.1763G> A (p.Arg588Gln)SNVPathogenicrs121908569GRCh37Chr 2, 88882948: 88882948
6EIF2AK3NM_004836.6(EIF2AK3): c.2985+1G> ASNVPathogenicrs869025179GRCh37Chr 2, 88870391: 88870391
7EIF2AK3EIF2AK3, 4-BP DEL, 1563GAAAdeletionPathogenicChr na, -1: -1
8EIF2AK3NM_004836.6(EIF2AK3): c.994G> T (p.Glu332Ter)SNVPathogenicrs121908570GRCh37Chr 2, 88890344: 88890344
9KCNJ5NM_000890.3(KCNJ5): c.1159G> C (p.Gly387Arg)SNVPathogenicrs199830292GRCh37Chr 11, 128786525: 128786525

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
1cellular response to amino acid starvationGO:003419810.1EIF2AK3, EIF2S1
2negative regulation of translational initiation in response to stressGO:003205710.0EIF2AK3, EIF2S1
3PERK-mediated unfolded protein responseGO:003649910.0EIF2AK3, EIF2S1
4protein autophosphorylationGO:00467779.9EIF2AK3, EIF2S1
5endocrine pancreas developmentGO:00310189.7EIF2AK3, PAX4
6response to endoplasmic reticulum stressGO:00349769.4EIF2AK3, EIF2S1
7response to manganese-induced endoplasmic reticulum stressGO:19907379.4EIF2AK3, EIF2S1

Sources for Wolcott-Rallison Syndrome

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
27GTR
28HGMD
29HMDB
30ICD10
31ICD10 via Orphanet
32ICD9CM
33IUPHAR
34KEGG
37MedGen
39MeSH
40MESH via Orphanet
41MGI
44NCI
45NCIt
46NDF-RT
49NINDS
50Novoseek
52OMIM
53OMIM via Orphanet
57PubMed
58QIAGEN
63SNOMED-CT via Orphanet
67Tumor Gene Family of Databases
68UMLS
69UMLS via Orphanet