Neurologic Waardenburg-Shah syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: WAARDENBURG-SHAH SYNDROME, NEUROLOGIC VARIANT
PCWH
WS4 plus
Peripheral demyelinating neuropathy - central dysmyelinating leukodystrophy - Waardenburg syndrome - Hirschsprung disease
Number of Symptoms 74
OrphanetNr: 163746
OMIM Id: 609136
ICD-10: E75.2
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: < 30 cases [Orphanet]
Inheritance: Autosomal dominant
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Congenital intestinal motility disorder
 -Rare gastroenterologic disease
 -Rare genetic disease
Genetic hypopigmentation of the skin
 -Rare genetic disease
Genetic peripheral neuropathy
 -Rare genetic disease
 -Rare neurologic disease
Hypopigmentation of the skin
 -Rare skin disease
Leukodystrophy
 -Rare genetic disease
 -Rare neurologic disease
Pigmentation disorder with eye involvement, excluding albinism
 -Rare eye disease
 -Rare genetic disease
Syndromic genetic deafness
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare otorhinolaryngologic disease
Syndromic intestinal malformation
 -Rare abdominal surgical disease
 -Rare developmental defect during embryogenesis
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000028) Cryptorchidism 347 / 7739
2
 (HPO:0100684) Salivary gland neoplasm Occasional [Orphanet] 4 / 7739
3
 (HPO:0000445) Wide nose Frequent [Orphanet] 190 / 7739
4
 (HPO:0000534) Abnormality of the eyebrow Frequent [Orphanet] 39 / 7739
5
 (HPO:0000606) Abnormality of the periorbital region Frequent [Orphanet] 96 / 7739
6
 (HPO:0002226) White eyebrow 10 / 7739
7
 (HPO:0000430) Underdeveloped nasal alae Frequent [Orphanet] 90 / 7739
8
 (HPO:0000426) Prominent nasal bridge Frequent [Orphanet] 121 / 7739
9
 (HPO:0002227) White eyelashes 11 / 7739
10
 (HPO:0000506) Telecanthus Occasional [Orphanet] 156 / 7739
11
 (HPO:0000458) Anosmia 49 / 7739
12
 (HPO:0000639) Nystagmus Very frequent [Orphanet] 555 / 7739
13
 (HPO:0001100) Heterochromia iridis Very frequent [Orphanet] 31 / 7739
14
 (HPO:0000522) Alacrima 14 / 7739
15
 (HPO:0008527) Congenital sensorineural hearing impairment 165 / 7739
16
 (HPO:0008625) Severe sensorineural hearing impairment 150 / 7739
17
 (HPO:0011382) Hypoplasia of the semicircular canal 2 / 7739
18
 (HPO:0000407) Sensorineural hearing impairment Very frequent [Orphanet] 524 / 7739
19
 (HPO:0004463) Absent brainstem auditory responses 2 / 7739
20
 (HPO:0001276) Hypertonia Very frequent [Orphanet] 317 / 7739
21
 (HPO:0009830) Peripheral neuropathy Very frequent [Orphanet] 206 / 7739
22
 (HPO:0002271) Autonomic dysregulation 11 / 7739
23
 (HPO:0001250) Seizures Very frequent [Orphanet] 1245 / 7739
24
 (HPO:0001249) Intellectual disability 1089 / 7739
25
 (HPO:0001263) Global developmental delay 853 / 7739
26
 (HPO:0011285) Long-segment aganglionic megacolon 1 / 7739
27
 (HPO:0011096) Peripheral demyelination 28 / 7739
28
 (HPO:0002251) Aganglionic megacolon Very frequent [Orphanet] 78 / 7739
29
 (HPO:0001251) Ataxia 413 / 7739
30
 (HPO:0001284) Areflexia 198 / 7739
31
 (HPO:0002510) Spastic tetraplegia 54 / 7739
32
 (HPO:0001265) Hyporeflexia 208 / 7739
33
 (HPO:0007182) Peripheral hypomyelination 7 / 7739
34
 (HPO:0002066) Gait ataxia Very frequent [Orphanet] 327 / 7739
35
 (HPO:0002313) Spastic paraparesis 33 / 7739
36
 (HPO:0004336) Myelin outfoldings 4 / 7739
37
 (HPO:0000762) Decreased nerve conduction velocity 36 / 7739
38
 (HPO:0002936) Distal sensory impairment 96 / 7739
39
 (HPO:0007256) Abnormal pyramidal signs Very frequent [Orphanet] 116 / 7739
40
 (HPO:0007108) Demyelinating peripheral neuropathy 8 / 7739
41
 (HPO:0008373) Puberty and gonadal disorders Frequent [Orphanet] 156 / 7739
42
 (HPO:0001761) Pes cavus 225 / 7739
43
 (HPO:0002803) Congenital contracture Occasional [Orphanet] 45 / 7739
44
 (HPO:0002240) Hepatomegaly Occasional [Orphanet] 467 / 7739
45
 (HPO:0002027) Abdominal pain Very frequent [Orphanet] 184 / 7739
46
 (HPO:0001744) Splenomegaly Occasional [Orphanet] 337 / 7739
47
 (HPO:0002019) Constipation Very frequent [Orphanet] 194 / 7739
48
 (HPO:0005214) Intestinal obstruction Very frequent [Orphanet] 35 / 7739
49
 (HPO:0002211) White forelock 18 / 7739
50
 (HPO:0001053) Hypopigmented skin patches Very frequent [Orphanet] 80 / 7739
51
 (HPO:0005599) Hypopigmentation of hair Frequent [Orphanet] 38 / 7739
52
 (HPO:0002216) Premature graying of hair Frequent [Orphanet] 43 / 7739
53
 (HPO:0011675) Arrhythmia Occasional [Orphanet] 226 / 7739
54
 (HPO:0004370) Abnormality of temperature regulation Occasional [Orphanet] 58 / 7739
55
 (HPO:0002460) Distal muscle weakness 122 / 7739
56
 (HPO:0003693) Distal amyotrophy 118 / 7739
57
 (HPO:0001319) Neonatal hypotonia 101 / 7739
58
 (HPO:0001252) Muscular hypotonia Very frequent [Orphanet] 990 / 7739
59
 (OMIM) Distal muscle weakness due to peripheral neuropathy 4 / 7739
60
 (OMIM) Sural nerve biopsy shows hypomyelination/demyelination 1 / 7739
61
 (HPO:0000006) Autosomal dominant inheritance 2518 / 7739
62
 (OMIM) Bright blue eyes 3 / 7739
63
 (OMIM) Vestibular malformation seen on temporal bone CT (in some patients) 1 / 7739
64
 (OMIM) Intestinal aganglionosis 1 / 7739
65
 (OMIM) Distal muscle wasting due to peripheral neuropathy 2 / 7739
66
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
67
 (OMIM) Hirschsprung disease, long-segment 1 / 7739
68
 (MedDRA:10067601) Dysmyelination 5 / 7739
69
 (HPO:0007266) Cerebral dysmyelination 13 / 7739
70
 (OMIM) Chronic intestinal pseudoobstruction 4 / 7739
71
 (HPO:0006978) Dysmyelinating leukodystrophy 2 / 7739
72
 (HPO:0012851) Colonic stenosis Frequent [Orphanet] 3 / 7739
73
 (OMIM) Sural nerve biopsy shows excessive focal folding of myelin sheaths 1 / 7739
74
 (OMIM) Decreased myenteric and submucosal ganglia in the bowel 4 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) The neurologic variant of Waardenburg-Shah syndrome is a complex neurocristopathy that includes features of 4 distinct syndromes: peripheral demyelinating neuropathy (see 118200), central dysmyelination, Waardenburg syndrome, and Hirschsprung disease (see 142623) (Inoue et al., 2004). Inoue et al. ...
Clinical Description OMIM Inoue et al. (1999) reported an 11-year-old Japanese girl with Waardenburg-Shah syndrome and neurologic abnormalities, including severe leukodystrophy suggestive of Pelizaeus-Merzbacher disease (312080) and peripheral neuropathy consistent with Charcot-Marie-Tooth disease type I (see 118200). The patient was born ...
Genotype-Phenotype Correlations OMIM In addition to causing the neurologic variant of Waardenburg-Shah syndrome, mutations in the SOX10 gene also cause Waardenburg-Shah syndrome (277580), which has a more restricted phenotype. Inoue et al. (2004) reported that although all nonsense and frameshift mutations ...
Molecular genetics OMIM In 3 patients with the neurologic variant of Waardenburg-Shah syndrome, Touraine et al. (2000) identified heterozygosity for 1 of 2 truncating mutations in the SOX10 gene: tyr313 to ter (Y313X; 602229.0006) or ser251 to ter (S251X; 602229.0007). The ...