Wolfram syndrome 2

General Information (adopted from Orphanet):

Synonyms, Signs: WFS2
Number of Symptoms 44
OrphanetNr:
OMIM Id: 604928
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
10739754 [IBIS]
Age of onset: Childhood
10739754 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Wolfram syndrome
 -Rare developmental defect during embryogenesis
 -Rare endocrine disease
 -Rare eye disease
 -Rare genetic disease
 -Rare otorhinolaryngologic disease

Comment:

The causative gene, CISD2, has been identified in patients with a type of Wolfram syndrome (WS2) resulting in early optic atrophy, diabetes mellitus, deafness, decreased lifespan, but not diabetes insipidus. The CISD2-encoded protein ERIS (endoplasmic reticulum intermembrane small protein) localizes to ER, but does not interact directly with wolframin. ERIS maps to chromosome 4q22 (PMID:22790102). Our patient does not show optic atrophy, one of the main diagnostic criteria for WFS, but optic neuropathy. Since the “asymptomatic” optic atrophy described in Jordanian patients is not completely supported, we could suppose that the ocular pathology in Jordanian patients was probably optic neuropathy and not optic atrophy. Therefore, as optic atrophy is required as main diagnostic criteria of WFS, it might be that the so-called WFS2 could not be a subtype of WFS (PMID:25056293).

Symptom Information: Sort by abundance 

1
 (HPO:0001892) Abnormal bleeding 22790102 IBIS 85 / 7739
2
 (HPO:0002239) Gastrointestinal hemorrhage 22790102 IBIS 97 / 7739
3
 (HPO:0000648) Optic atrophy 22790102; 10739754; 17846994; 25371195 IBIS 238 / 7739
4
 (HPO:0001138) Optic neuropathy 25056293 IBIS 12 / 7739
5
 (HPO:0007641) Dyschromatopsia 25056293 IBIS 19 / 7739
6
 (HPO:0000505) Visual impairment 10739754 IBIS 297 / 7739
7
 (HPO:0001928) Abnormality of coagulation 22790102 IBIS 44 / 7739
8
 (HPO:0001935) Microcytic anemia 25371195 IBIS 32 / 7739
9
 (HPO:0004313) Decreased antibody level in blood 25371195 IBIS 47 / 7739
10
 (HPO:0100851) Abnormal emotion/affect behavior 25371195 IBIS 85 / 7739
11
 (HPO:0000716) Depression 17846994 IBIS 99 / 7739
12
 (HPO:0100716) Self-injurious behavior 17846994 IBIS 43 / 7739
13
 (MedDRA:10065604) Suicidal behaviour 17846994 IBIS 3 / 7739
14
 (HPO:0001370) Rheumatoid arthritis 25371195 IBIS 12 / 7739
15
 (HPO:0002588) Duodenal ulcer 25371195 IBIS 15 / 7739
16
 (HPO:0002566) Intestinal malrotation 25056293 IBIS 89 / 7739
17
 (HPO:0002576) Intussusception 25056293 IBIS 10 / 7739
18
 (HPO:0004398) Peptic ulcer 10739754; 25371195 IBIS 7 / 7739
19
 (HPO:0012569) Delayed menarche 25371195 IBIS 5 / 7739
20
 (HPO:0000135) Hypogonadism 22790102; 25371195 IBIS 89 / 7739
21
 (HPO:0000786) Primary amenorrhea 25371195 IBIS 61 / 7739
22
 (HPO:0000140) Abnormality of the menstrual cycle 25371195 IBIS 7 / 7739
23
 (HPO:0000876) Oligomenorrhea 25371195 IBIS 13 / 7739
24
 (HPO:0000271) Abnormality of the face 22790102 IBIS 108 / 7739
25
 (HPO:0001999) Abnormal facial shape 10739754 IBIS 169 / 7739
26
 (HPO:0000407) Sensorineural hearing impairment 25056293 IBIS 524 / 7739
27
 (HPO:0001757) High-frequency sensorineural hearing impairment 10739754; 17846994; 25056293 IBIS 7 / 7739
28
 (HPO:0000079) Abnormality of the urinary system 22790102; 10739754 IBIS 88 / 7739
29
 (HPO:0000011) Neurogenic bladder 25371195 IBIS 11 / 7739
30
 (HPO:0000103) Polyuria 25371195 IBIS 60 / 7739
31
 (HPO:0003774) Stage 5 chronic kidney disease 10739754; 17846994 IBIS 78 / 7739
32
 (HPO:0000083) Renal insufficiency 22790102; 10739754 IBIS 232 / 7739
33
 (HPO:0004866) Impaired ADP-induced platelet aggregation 25056293 IBIS 4 / 7739
34
 (HPO:0008320) Impaired collagen-induced platelet aggregation 22790102 IBIS 4 / 7739
35
 (HPO:0000873) Diabetes insipidus 25371195 IBIS 34 / 7739
36
 (HPO:0000819) Diabetes mellitus 22790102; 10739754; 17846994; 25056293; 25371195 IBIS 131 / 7739
37
 (HPO:0000365) Hearing impairment 22790102; 10739754 IBIS 539 / 7739
38
 (HPO:0005101) High-frequency hearing impairment 25371195 IBIS 16 / 7739
39
 (HPO:0002878) Respiratory failure 10739754 IBIS 57 / 7739
40
 (MedDRA:10002556) Ankylosing spondylitis 25371195 IBIS 2 / 7739
41
 (MedDRA:10061459) Gastrointestinal ulcer 22790102 IBIS 1 / 7739
42
 (MedDRA:10022714) Intestinal ulcer 25056293 IBIS 1 / 7739
43
 (MedDRA:10039486) Sarcoidosis 25371195 IBIS 1 / 7739
44
 (OMIM) Central respiratory failure 10739754 IBIS 2 / 7739

Associated genes:

CISD2;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Although Wolfram syndrome (222300) is also referred to as DIDMOAD (for diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), only insulin-dependent diabetes mellitus and optic atrophy are considered necessary to make the diagnosis. One form of Wolfram syndrome ...
Molecular genetics OMIM Amr et al. (2007) identified a single missense mutation in the CISD2 gene (611507), in 3 consanguineous families of Jordanian descent with Wolfram syndrome studied by El-Shanti et al. (2000). A G-to-C transversion at nucleotide 109 predicted an ...