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, 30ICD10 via Orphanet, 36MedGen, 38MeSH, 39MESH via Orphanet, 47NIH Rare Diseases, 49Novoseek, 51OMIM, 53Orphanet, 63The Human Phenotype Ontology, 67UMLS, 68UMLS via Orphanet, 69UniProtKB/Swiss-Prot
See all MalaCards sources

Aliases & Descriptions for Wolcott-Rallison Syndrome:

Name: Wolcott-Rallison Syndrome 51 24 53 69 12 49 67
Multiple Epiphyseal Dysplasia with Early-Onset Diabetes Mellitus 24 69
Iddm-Med Syndrome 47 69
Med-Iddm Syndrome 47 69
Wrs 53 69
 
Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus 51
Early-Onset Diabetes Mellitus with Multiple Epiphyseal Dysplasia 53
Epiphyseal Dysplasia Multiple with Early-Onset Diabetes Mellitus 47
Wolcott Rallison Syndrome 47
Romano-Ward Syndrome 67

Characteristics:

Orphanet epidemiological data:

53
wolcott-rallison syndrome:
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal

HPO:

63
wolcott-rallison syndrome:
Inheritance: autosomal recessive inheritance
Onset and clinical course: infantile onset

Classifications:



External Ids:

OMIM51 226980
Orphanet53 ORPHA1667
MESH via Orphanet39 C536739
UMLS via Orphanet68 C0432217
ICD10 via Orphanet30 E13
MedGen36 C0432217
MeSH38 D010009

Summaries for Wolcott-Rallison Syndrome

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OMIM:51 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:69 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 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:

 63 53 (show all 87)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of the metaphyses63 53 hallmark (90%) Very frequent (99-80%) HP:0000944
2 short stature63 53 hallmark (90%) Very frequent (99-80%) HP:0004322
3 type ii diabetes mellitus63 hallmark (90%) HP:0005978
4 platyspondyly63 53 typical (50%) Frequent (79-30%) HP:0000926
5 brachydactyly syndrome63 53 typical (50%) Frequent (79-30%) HP:0001156
6 gait disturbance63 53 typical (50%) Frequent (79-30%) HP:0001288
7 abnormality of neutrophils63 typical (50%) HP:0001874
8 hepatomegaly63 53 typical (50%) Frequent (79-30%) HP:0002240
9 delayed skeletal maturation63 53 typical (50%) Frequent (79-30%) HP:0002750
10 genu valgum63 53 typical (50%) Frequent (79-30%) HP:0002857
11 elevated hepatic transaminases63 53 typical (50%) Frequent (79-30%) HP:0002910
12 acute hepatic failure63 53 typical (50%) Frequent (79-30%) HP:0006554
13 short thorax63 53 typical (50%) Frequent (79-30%) HP:0010306
14 abnormality of immune system physiology63 typical (50%) HP:0010978
15 cognitive impairment63 typical (50%) HP:0100543
16 chronic hepatic failure63 53 typical (50%) Frequent (79-30%) HP:0100626
17 renal insufficiency63 53 occasional (7.5%) Occasional (29-5%) HP:0000083
18 nephropathy63 53 occasional (7.5%) Occasional (29-5%) HP:0000112
19 microcephaly63 53 occasional (7.5%) Occasional (29-5%) HP:0000252
20 hypothyroidism63 53 occasional (7.5%) Occasional (29-5%) HP:0000821
21 seizures63 53 occasional (7.5%) Occasional (29-5%) HP:0001250
22 intrauterine growth retardation63 53 occasional (7.5%) Occasional (29-5%) HP:0001511
23 exocrine pancreatic insufficiency63 53 occasional (7.5%) Occasional (29-5%) HP:0001738
24 hypoglycemia63 53 occasional (7.5%) Occasional (29-5%) HP:0001943
25 abnormality of neuronal migration63 53 occasional (7.5%) Occasional (29-5%) HP:0002269
26 recurrent fractures63 53 occasional (7.5%) Occasional (29-5%) HP:0002757
27 kyphosis63 53 occasional (7.5%) Occasional (29-5%) HP:0002808
28 hyperlordosis63 53 occasional (7.5%) Occasional (29-5%) HP:0003307
29 aplasia/hypoplasia of the pancreas63 occasional (7.5%) HP:0100800
30 high palate63 HP:0000218
31 hypertelorism63 HP:0000316
32 upslanted palpebral fissure63 HP:0000582
33 insulin-resistant diabetes mellitus63 HP:0000831
34 osteoporosis63 53 Very frequent (99-80%) HP:0000939
35 global developmental delay63 HP:0001263
36 hypertonia63 HP:0001276
37 carpal bone hypoplasia63 HP:0001498
38 barrel-shaped chest63 HP:0001552
39 multiple epiphyseal dysplasia63 53 Very frequent (99-80%) HP:0002654
40 epiphyseal dysplasia63 53 Very frequent (99-80%) HP:0002656
41 coxa valga63 53 Frequent (79-30%) HP:0002673
42 hip dislocation63 53 Frequent (79-30%) HP:0002827
43 narrow iliac wings63 53 Frequent (79-30%) HP:0002868
44 flattened epiphysis63 HP:0003071
45 irregular vertebral endplates63 HP:0003301
46 hypoplasia of the odontoid process63 HP:0003311
47 irregular carpal bones63 HP:0004236
48 preauricular pit63 HP:0004467
49 depressed nasal bridge63 HP:0005280
50 shortening of all middle phalanges of the fingers63 HP:0006110
51 reduced pancreatic beta cells63 53 Occasional (29-5%) HP:0006274
52 irregular tarsal ossification63 HP:0008134
53 ivory epiphyses of the toes63 HP:0010168
54 cone-shaped epiphyses of the phalanges of the hand63 53 Very frequent (99-80%) HP:0010230
55 ivory epiphyses of the phalanges of the hand63 HP:0010234
56 small epiphyses63 HP:0010585
57 hip subluxation63 HP:0030043
58 renal tubular dysfunction53 Very frequent (99-80%)
59 thin vermilion border53 Very frequent (99-80%)
60 epicanthus53 Very frequent (99-80%)
61 triangular face53 Very frequent (99-80%)
62 high forehead53 Very frequent (99-80%)
63 hypermetropia53 Very frequent (99-80%)
64 microdontia53 Very frequent (99-80%)
65 osteopenia53 Very frequent (99-80%)
66 death in infancy53 Very frequent (99-80%)
67 weight loss53 Very frequent (99-80%)
68 dehydration53 Very frequent (99-80%)
69 hyperuricemia53 Very frequent (99-80%)
70 steatorrhea53 Very frequent (99-80%)
71 hyperglycemia53 Very frequent (99-80%)
72 glycosuria53 Very frequent (99-80%)
73 abnormality of epiphysis morphology53 Very frequent (99-80%)
74 transient neonatal diabetes mellitus53 Very frequent (99-80%)
75 abnormality of pancreas morphology53 Very frequent (99-80%)
76 intellectual disability53 Frequent (79-30%)
77 muscular hypotonia53 Frequent (79-30%)
78 motor delay53 Frequent (79-30%)
79 abnormal heart morphology53 Frequent (79-30%)
80 neutropenia53 Frequent (79-30%)
81 ketoacidosis53 Frequent (79-30%)
82 intracerebral periventricular calcifications53 Frequent (79-30%)
83 neurodevelopmental delay53 Frequent (79-30%)
84 enlarged thorax53 Frequent (79-30%)
85 jaundice53 Occasional (29-5%)
86 pancreatic hypoplasia53 Occasional (29-5%)
87 coma53 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:

35
Bone, Pancreas, Liver, Neutrophil, Heart, Kidney

Animal Models for Wolcott-Rallison Syndrome or affiliated genes

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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:

69
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
1response to manganese-induced endoplasmic reticulum stressGO:19907379.9EIF2AK3, EIF2S1
2negative regulation of translational initiation in response to stressGO:00320579.9EIF2AK3, EIF2S1
3endocrine pancreas developmentGO:00310189.6EIF2AK3, PAX4
4cellular response to amino acid starvationGO:00341989.5EIF2AK3, EIF2S1
5protein autophosphorylationGO:00467779.4EIF2AK3, EIF2S1
6response to endoplasmic reticulum stressGO:00349769.4EIF2AK3, EIF2S1
7PERK-mediated unfolded protein responseGO:00364999.1EIF2AK3, EIF2S1

Sources for Wolcott-Rallison Syndrome

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
26GTR
27HGMD
28HMDB
29ICD10
30ICD10 via Orphanet
31ICD9CM
32IUPHAR
33KEGG
36MedGen
38MeSH
39MESH via Orphanet
40MGI
43NCI
44NCIt
45NDF-RT
48NINDS
49Novoseek
51OMIM
52OMIM via Orphanet
56PubMed
57QIAGEN
62SNOMED-CT via Orphanet
66Tumor Gene Family of Databases
67UMLS
68UMLS via Orphanet