Wolfram syndrome 1

General Information (adopted from Orphanet):

Synonyms, Signs: DIDMOAD
WFS1
WFS
Diabetes insipidus and mellitus with optic atrophy and deafness
Number of Symptoms 165
OrphanetNr:
OMIM Id: 222300
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: <= 0.14 of 100 000 - PMID: 23429432 [IBIS]
Inheritance: Monogenic
Autosomal recessive
- PMID: 23981289 [IBIS]
Age of onset: Childhood
- PMID: 23981289 [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:

Wolfram syndrome 1 (WS1) is an autosomal recessive disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DI DM OA D syndrome) associated with other variable clinical manifestations. The causative gene for WS1 (WFS1) encoding wolframin maps to chromosome 4p16.1. Wolframin has an important function in maintaining the homeostasis of the endoplasmic reticulum (ER) in pancreatic beta cells. Diabetes mellitus, a nearly constant finding, is the first manifestation to occur. Nonautoimmune and non-HLA-linked diabetes mellitus presents at an average age of 6 years (range 3 weeks to 16 years) and is characterized by rare microvascular complications that seem to develop more slowly than in the more common type 1 diabetes mellitus. A decreased tendency of these patients to develop ketoacidosis has been reported. Almost all patients require insulin replacement (PMID:22790102). Because WFS is a progressive disorder, affected individuals experience a wide spectrum of symptoms during their lifetimes. The lifespans of affected individuals are generally shortened as a consequence of neuropsychiatric problems, such as central respiratory failure, food aspiration and suicide (PMID:25211237).

Symptom Information: Sort by abundance 

1
 (HPO:0002019) Constipation 23981289; 26742931 IBIS 194 / 7739
2
 (HPO:0012450) Chronic constipation 24890733 IBIS 10 / 7739
3
 (HPO:0002014) Diarrhea 26742931 IBIS 225 / 7739
4
 (HPO:0000568) Microphthalmia 25255707 IBIS 183 / 7739
5
 (HPO:0007686) Abnormal pupillary function 23373429 IBIS 3 / 7739
6
 (HPO:0007695) Abnormal pupillary light reflex 22790102 IBIS 2 / 7739
7
 (HPO:0000518) Cataract 23981289; 22790102; 26742931; 24890733; 21564155 IBIS 454 / 7739
8
 (HPO:0010698) Nuclear pulverulent cataract 23373429 IBIS 1 / 7739
9
 (HPO:0010693) Pulverulent cataract 23373429 IBIS 6 / 7739
10
 (HPO:0000587) Abnormality of the optic nerve 22790102 IBIS 5 / 7739
11
 (HPO:0007766) Optic disc hypoplasia 25255707 IBIS 7 / 7739
12
 (HPO:0000609) Optic nerve hypoplasia 25255707 IBIS 26 / 7739
13
 (HPO:0000648) Optic atrophy Very frequent [IBIS] 23981289; 22790102; 25211237; 26742931; 25173644; 24890733; 23595122; 23429432; 23338790; 22792385; 21564155 IBIS 238 / 7739
14
 (HPO:0000543) Optic disc pallor 23981289; 24117146; 23373429 IBIS 67 / 7739
15
 (HPO:0008002) Abnormality of macular pigmentation 22790102 IBIS 20 / 7739
16
 (HPO:0000580) Pigmentary retinopathy 22790102 IBIS 49 / 7739
17
 (HPO:0000488) Retinopathy 21564155 IBIS 75 / 7739
18
 (HPO:0000639) Nystagmus 23981289; 22790102; 23429432 IBIS 555 / 7739
19
 (HPO:0000666) Horizontal nystagmus 22792385 IBIS 32 / 7739
20
 (HPO:0000486) Strabismus 24117146 IBIS 576 / 7739
21
 (HPO:0000577) Exotropia 25255707; 23373429 IBIS 43 / 7739
22
 (HPO:0000551) Abnormality of color vision 23981289; 22792385 IBIS 20 / 7739
23
 (HPO:0007641) Dyschromatopsia 26742931; 22792385 IBIS 19 / 7739
24
 (HPO:0007994) Peripheral visual field loss 26742931; 25173644 IBIS 13 / 7739
25
 (HPO:0000505) Visual impairment 24117146 IBIS 297 / 7739
26
 (HPO:0000646) Amblyopia 24890733 IBIS 42 / 7739
27
 (HPO:0000529) Progressive visual loss 23338790 IBIS 54 / 7739
28
 (HPO:0000501) Glaucoma 22790102; 24890733; 23373429 IBIS 180 / 7739
29
 (HPO:0001953) Diabetic ketoacidosis 23981289 IBIS 6 / 7739
30
 (HPO:0004322) Short stature 22790102; 24890733; 21564155 IBIS 1232 / 7739
31
 (HPO:0002173) Hypoglycemic seizures 23981289 IBIS 19 / 7739
32
 (HPO:0001629) Ventricular septal defect 22790102 IBIS 316 / 7739
33
 (HPO:0001637) Abnormality of the myocardium 22790102 IBIS 76 / 7739
34
 (HPO:0001638) Cardiomyopathy 21564155 IBIS 192 / 7739
35
 (HPO:0001644) Dilated cardiomyopathy 22790102 IBIS 141 / 7739
36
 (HPO:0002119) Ventriculomegaly 25255707 IBIS 253 / 7739
37
 (HPO:0001642) Pulmonic stenosis 22790102 IBIS 89 / 7739
38
 (HPO:0001636) Tetralogy of Fallot 22790102 IBIS 104 / 7739
39
 (HPO:0000822) Hypertension 21564155 IBIS 224 / 7739
40
 (HPO:0001278) Orthostatic hypotension 26742931 IBIS 24 / 7739
41
 (HPO:0000824) Growth hormone deficiency 22790102; 24890733 IBIS 56 / 7739
42
 (HPO:0001889) Megaloblastic anemia 21564155 IBIS 28 / 7739
43
 (HPO:0000010) Recurrent urinary tract infections 22790102; 26742931 IBIS 56 / 7739
44
 (HPO:0003228) Hypernatremia 25255707 IBIS 12 / 7739
45
 (HPO:0002902) Hyponatremia 26742931 IBIS 37 / 7739
46
 (HPO:0001336) Myoclonus 22790102 IBIS 115 / 7739
47
 (HPO:0003739) Myoclonic spasms 22790102 IBIS 7 / 7739
48
 (HPO:0002459) Dysautonomia 26742931; 21564155 IBIS 34 / 7739
49
 (HPO:0000224) Decreased taste sensation 23981289; 26742931 IBIS 6 / 7739
50
 (HPO:0004408) Abnormality of the sense of smell 23981289; 26742931 IBIS 28 / 7739
51
 (HPO:0000458) Anosmia 23981289; 22790102 IBIS 49 / 7739
52
 (HPO:0004409) Hyposmia 23981289 IBIS 16 / 7739
53
 (HPO:0002495) Impaired vibratory sensation 23981289; 22792385 IBIS 26 / 7739
54
 (HPO:0001251) Ataxia 26742931; 24890733; 23429432; 21564155 IBIS 413 / 7739
55
 (HPO:0002066) Gait ataxia 22792385 IBIS 327 / 7739
56
 (HPO:0002470) Nonprogressive cerebellar ataxia 22790102; 25173644; 24890733 IBIS 4 / 7739
57
 (HPO:0002078) Truncal ataxia 22790102 IBIS 41 / 7739
58
 (HPO:0002311) Incoordination 22792385 IBIS 84 / 7739
59
 (HPO:0000708) Behavioral abnormality 22790102; 25211237; 23595122; 23429432 IBIS 212 / 7739
60
 (HPO:0100710) Impulsivity 22792385 IBIS 16 / 7739
61
 (HPO:0000720) Mood swings 26742931 IBIS 6 / 7739
62
 (HPO:0000718) Aggressive behavior 22790102; 22792385 IBIS 109 / 7739
63
 (HPO:0000739) Anxiety 26742931; 24890733; 22792385 IBIS 67 / 7739
64
 (MedDRA:10033664) Panic attack 26742931 IBIS 2 / 7739
65
 (HPO:0007018) Attention deficit hyperactivity disorder 25211237 IBIS 56 / 7739
66
 (MedDRA:10064478) Conduct disorder 22792385 IBIS 1 / 7739
67
 (HPO:0001328) Specific learning disability 24890733; 23373429; 21564155 IBIS 114 / 7739
68
 (HPO:0001260) Dysarthria 26742931 IBIS 329 / 7739
69
 (HPO:0002344) Progressive neurologic deterioration 26742931 IBIS 27 / 7739
70
 (HPO:0001270) Motor delay 24890733 IBIS 322 / 7739
71
 (HPO:0000716) Depression 22790102; 26742931; 25173644; 24117146; 22792385; 21564155 IBIS 99 / 7739
72
 (HPO:0008765) Auditory hallucinations 23981289 IBIS 8 / 7739
73
 (HPO:0012378) Fatigue 26742931 IBIS 50 / 7739
74
 (MedDRA:10002368) Anger 24890733 IBIS 1 / 7739
75
 (HPO:0000722) Obsessive-compulsive behavior 23981289 IBIS 35 / 7739
76
 (HPO:0000709) Psychosis 22790102; 26742931 IBIS 61 / 7739
77
 (HPO:0100786) Hypersomnia 26742931 IBIS 4 / 7739
78
 (HPO:0100785) Insomnia 24890733 IBIS 18 / 7739
79
 (HPO:0000733) Stereotypy 23981289 IBIS 58 / 7739
80
 (MedDRA:10065604) Suicidal behaviour 23595122 IBIS 3 / 7739
81
 (HPO:0100543) Cognitive impairment 22790102; 21564155 IBIS 230 / 7739
82
 (HPO:0001288) Gait disturbance 23981289 IBIS 318 / 7739
83
 (HPO:0002080) Intention tremor 22792385 IBIS 44 / 7739
84
 (HPO:0002015) Dysphagia 26742931; 23429432 IBIS 301 / 7739
85
 (HPO:0002315) Headache 26742931 IBIS 175 / 7739
86
 (HPO:0001284) Areflexia 24890733 IBIS 198 / 7739
87
 (HPO:0001250) Seizures 22790102; 26742931 IBIS 1245 / 7739
88
 (HPO:0002373) Febrile seizures 23981289 IBIS 37 / 7739
89
 (HPO:0001511) Intrauterine growth retardation 25255707; 24890733 IBIS 358 / 7739
90
 (HPO:0001561) Polyhydramnios 25255707 IBIS 191 / 7739
91
 (HPO:0002079) Hypoplasia of the corpus callosum 25255707 IBIS 161 / 7739
92
 (HPO:0000970) Anhidrosis 26742931 IBIS 24 / 7739
93
 (HPO:0000975) Hyperhidrosis 26742931 IBIS 64 / 7739
94
 (HPO:0000966) Hypohidrosis 26742931 IBIS 41 / 7739
95
 (HPO:0004370) Abnormality of temperature regulation 26742931 IBIS 58 / 7739
96
 (HPO:0002045) Hypothermia 26742931 IBIS 27 / 7739
97
 (HPO:0002578) Gastroparesis 22790102; 26742931 IBIS 11 / 7739
98
 (HPO:0002607) Bowel incontinence 22790102 IBIS 33 / 7739
99
 (HPO:0001081) Cholelithiasis 22790102 IBIS 36 / 7739
100
 (HPO:0000135) Hypogonadism 26742931; 24890733 IBIS 89 / 7739
101
 (HPO:0000815) Hypergonadotropic hypogonadism 21564155 IBIS 48 / 7739
102
 (HPO:0000026) Male hypogonadism 22790102 IBIS 20 / 7739
103
 (HPO:0000478) Abnormality of the eye 23373429 IBIS 126 / 7739
104
 (HPO:0000140) Abnormality of the menstrual cycle 22790102 IBIS 7 / 7739
105
 (HPO:0012503) Abnormality of the pituitary gland 23981289 IBIS 2 / 7739
106
 (HPO:0011751) Abnormality of the posterior pituitary 22790102 IBIS 1 / 7739
107
 (HPO:0000863) Central diabetes insipidus 25255707 IBIS 7 / 7739
108
 (HPO:0000407) Sensorineural hearing impairment Frequent [IBIS] 26742931; 23595122; 23373429 IBIS 524 / 7739
109
 (HPO:0001757) High-frequency sensorineural hearing impairment 26742931; 24890733; 23338790 IBIS 7 / 7739
110
 (HPO:0008625) Severe sensorineural hearing impairment 26742931 IBIS 150 / 7739
111
 (HPO:0000707) Abnormality of the nervous system 22790102 IBIS 61 / 7739
112
 (HPO:0002104) Apnea 26742931 IBIS 106 / 7739
113
 (HPO:0002871) Central apnea 22790102; 26742931 IBIS 10 / 7739
114
 (HPO:0000821) Hypothyroidism 24890733 IBIS 141 / 7739
115
 (HPO:0011787) Central hypothyroidism 25255707 IBIS 4 / 7739
116
 (HPO:0000079) Abnormality of the urinary system Frequent [IBIS] 26742931 IBIS 88 / 7739
117
 (HPO:0010955) Dilatation of the bladder 25173644 IBIS 2 / 7739
118
 (HPO:0000009) Functional abnormality of the bladder 26742931 IBIS 2 / 7739
119
 (HPO:0000805) Enuresis 23981289; 24890733 IBIS 11 / 7739
120
 (HPO:0010677) Enuresis nocturna 21564155 IBIS 7 / 7739
121
 (HPO:0000011) Neurogenic bladder 23981289; 22790102; 26742931; 25173644; 25173644; 24890733; 23373429; 21564155 IBIS 11 / 7739
122
 (HPO:0000017) Nocturia 23981289; 25173644 IBIS 5 / 7739
123
 (HPO:0002839) Urinary bladder sphincter dysfunction 26742931 IBIS 34 / 7739
124
 (HPO:0000020) Urinary incontinence 22790102; 26742931; 25173644 IBIS 75 / 7739
125
 (HPO:0000016) Urinary retention 23981289; 22790102 IBIS 7 / 7739
126
 (HPO:0000076) Vesicoureteral reflux 25173644 IBIS 94 / 7739
127
 (HPO:0010935) Abnormality of the upper urinary tract 26742931 IBIS 3 / 7739
128
 (HPO:0000077) Abnormality of the kidney 23373429 IBIS 73 / 7739
129
 (HPO:0012210) Abnormal renal morphology 25211237; 23429432 IBIS 18 / 7739
130
 (HPO:0000126) Hydronephrosis 25173644; 23373429 IBIS 119 / 7739
131
 (HPO:0000103) Polyuria 25255707; 25173644 IBIS 60 / 7739
132
 (HPO:0009806) Nephrogenic diabetes insipidus 22790102 IBIS 8 / 7739
133
 (HPO:0012622) Chronic kidney disease 23981289 IBIS 32 / 7739
134
 (HPO:0000072) Hydroureter 22790102; 25173644 IBIS 146 / 7739
135
 (HPO:0006000) Ureteral obstruction 26742931 IBIS 3 / 7739
136
 (HPO:0001873) Thrombocytopenia 21564155 IBIS 224 / 7739
137
 (HPO:0000873) Diabetes insipidus Frequent [IBIS] 23981289; 22790102; 25211237; 26742931; 25173644; 23429432; 22792385; 21564155 IBIS 34 / 7739
138
 (HPO:0000819) Diabetes mellitus Very frequent [IBIS] 23981289; 22790102; 25211237; 26742931; 25173644; 24890733; 24117146; 23595122; 23429432; 23373429; 23338790; 22792385; 21564155 IBIS 131 / 7739
139
 (HPO:0000365) Hearing impairment Frequent [IBIS] 23981289; 22790102; 25211237; 25173644; 23429432; 22792385; 21564155 IBIS 539 / 7739
140
 (HPO:0005101) High-frequency hearing impairment 22790102 IBIS 16 / 7739
141
 (HPO:0001730) Progressive hearing impairment 23373429 IBIS 29 / 7739
142
 (HPO:3000030) Abnormality of bony orbit of skull 25255707 IBIS 1 / 7739
143
 (HPO:0001317) Abnormality of the cerebellum 25211237 IBIS 36 / 7739
144
 (HPO:0012444) Brain atrophy 22790102; 22792385 IBIS 24 / 7739
145
 (HPO:0001272) Cerebellar atrophy 22790102; 24890733 IBIS 197 / 7739
146
 (HPO:0001321) Cerebellar hypoplasia 23981289 IBIS 114 / 7739
147
 (HPO:0002059) Cerebral atrophy 26742931; 22790102 IBIS 171 / 7739
148
 (HPO:0030151) Cholangitis 22790102 IBIS 10 / 7739
149
 (HPO:0012785) Flexion contracture of finger 23373429 IBIS 3 / 7739
150
 (HPO:0002171) Gliosis 22790102 IBIS 48 / 7739
151
 (HPO:0040075) Hypopituitarism 22790102; 21564155 IBIS 32 / 7739
152
 (HPO:0002365) Hypoplasia of the brainstem 23981289 IBIS 41 / 7739
153
 (HPO:0012758) Neurodevelopmental delay 25255707 IBIS 949 / 7739
154
 (HPO:0006879) Pontocerebellar atrophy 24890733 IBIS 6 / 7739
155
 (HPO:0002878) Respiratory failure 23429432 IBIS 57 / 7739
156
 (HPO:0030329) Retinal thinning 26742931 IBIS 3 / 7739
157
 (HPO:0030211) Slow pupillary light response 23981289 IBIS 2 / 7739
158
 (HPO:0030532) Visual acuity test abnormality 23981289 IBIS 4 / 7739
159
 (MedDRA:10003497) Asphyxia 23429432 IBIS 2 / 7739
160
 (MedDRA:10012689) Diabetic retinopathy 22790102 IBIS 1 / 7739
161
 (MedDRA:10020741) Hyperpyrexia 26742931 IBIS 2 / 7739
162
 (MedDRA:10058560) Tandem gait test abnormal 22792385 IBIS 1 / 7739
163
 (OMIM) Brain stem atrophy 26742931 IBIS 3 / 7739
164
 (OMIM) Microspherophakia 23373429 IBIS 7 / 7739
165
 (OMIM) Urinary bladder atony 22790102; 26742931 IBIS 2 / 7739

Associated genes:

WFS1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Wolfram syndrome-1 is a rare and severe autosomal recessive neurodegenerative disease characterized by diabetes mellitus, optic atrophy, diabetes insipidus, and deafness (DIDMOAD). Additional clinical features may include renal abnormalities, ataxia, dementia or mental retardation, and diverse psychiatric illnesses. ...
Clinical Description OMIM Wolfram syndrome is sometimes referred to as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Wolfram and Wagener (1938) found juvenile diabetes mellitus and optic atrophy in 4 of 8 sibs. Tyrer (1943) observed 3 of 8 ...
Genotype-Phenotype Correlations OMIM Cano et al. (2007) studied 12 patients from 11 families with Wolfram syndrome and identified 8 novel and 7 previously described mutations in the WFS1 gene. In a metaanalysis of 5 published clinical and molecular studies of WFS1 ...
Molecular genetics OMIM Strom et al. (1998) identified loss-of-function mutations in both alleles of the WFS1 gene in patients with Wolfram syndrome. Homozygous mutations were found in 5 families; compound heterozygosity was found in 3 other families. In a ninth family, ...