X-linked Charcot-Marie-Tooth disease type 4

General Information (adopted from Orphanet):

Synonyms, Signs: CHARCOT-MARIE-TOOTH DISEASE WITH DEAFNESS AND MENTAL RETARDATION
NEUROPATHY, AXONAL MOTOR-SENSORY, WITH DEAFNESS AND MENTAL RETARDATION
CHARCOT-MARIE-TOOTH DISEASE, X-LINKED RECESSIVE, 4
NADMR
CMTX4
COWCK
NAMSD
CMT4X
Cowchock syndrome
Number of Symptoms 36
OrphanetNr: 101078
OMIM Id: 310490
ICD-10: G60.0
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: X-linked recessive
[Orphanet]
Age of onset: Childhood
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: X-linked Charcot-Marie-Tooth disease
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease
 -Rare otorhinolaryngologic disease
X-linked recessive hereditary axonal motor and sensory neuropathy
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0003236) Elevated serum creatine phosphokinase 214 / 7739
2
 (HPO:0003202) Skeletal muscle atrophy Very frequent [Orphanet] 281 / 7739
3
 (HPO:0001324) Muscle weakness Very frequent [Orphanet] 859 / 7739
4
 (HPO:0003134) Abnormality of peripheral nerve conduction Very frequent [Orphanet] 38 / 7739
5
 (HPO:0007002) Motor axonal neuropathy 17 / 7739
6
 (HPO:0000763) Sensory neuropathy 78 / 7739
7
 (HPO:0003474) Sensory impairment Very frequent [Orphanet] 54 / 7739
8
 (HPO:0007021) Pain insensitivity Frequent [Orphanet] 35 / 7739
9
 (HPO:0002936) Distal sensory impairment 96 / 7739
10
 (HPO:0003390) Sensory axonal neuropathy 26 / 7739
11
 (HPO:0009830) Peripheral neuropathy Very frequent [Orphanet] 206 / 7739
12
 (HPO:0011442) Abnormality of central motor function Frequent [Orphanet] 76 / 7739
13
 (HPO:0002066) Gait ataxia Occasional [Orphanet] 327 / 7739
14
 (HPO:0001249) Intellectual disability 1089 / 7739
15
 (HPO:0002360) Sleep disturbance Occasional [Orphanet] 113 / 7739
16
 (HPO:0100543) Cognitive impairment rare [HPO:skoehler] 230 / 7739
17
 (HPO:0002167) Neurological speech impairment Occasional [Orphanet] 308 / 7739
18
 (HPO:0001288) Gait disturbance Occasional [Orphanet] 318 / 7739
19
 (HPO:0001337) Tremor Occasional [Orphanet] 200 / 7739
20
 (HPO:0001315) Reduced tendon reflexes Very frequent [Orphanet] 160 / 7739
21
 (HPO:0001761) Pes cavus Very frequent [Orphanet] 225 / 7739
22
 (HPO:0010488) Aplasia/Hypoplasia of the palmar creases Very frequent [Orphanet] 15 / 7739
23
 (HPO:0002808) Kyphosis Frequent [Orphanet] 289 / 7739
24
 (HPO:0002650) Scoliosis Frequent [Orphanet] 705 / 7739
25
 (HPO:0000407) Sensorineural hearing impairment rare [HPO:skoehler] 524 / 7739
26
 (HPO:0008527) Congenital sensorineural hearing impairment 165 / 7739
27
 (HPO:0008625) Severe sensorineural hearing impairment 150 / 7739
28
 (HPO:0000365) Hearing impairment Frequent [Orphanet] 539 / 7739
29
 (HPO:0012758) Neurodevelopmental delay Frequent [Orphanet] 949 / 7739
30
 (HPO:0001419) X-linked recessive inheritance 189 / 7739
31
 (OMIM) Distal muscle wasting due to peripheral neuropathy 2 / 7739
32
 (OMIM) Distal muscle weakness due to peripheral neuropathy 4 / 7739
33
 (OMIM) Increased numbers of abnormally-shaped mitochondria in subsarcolemmal areas 1 / 7739
34
 (OMIM) Increased serum transaminases 2 / 7739
35
 (OMIM) Neurogenic atrophy see on muscle biopsy 4 / 7739
36
 (OMIM) T2-weighted hyperintensities in the supratentorial white matter seen on brain MRI 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Cowchock syndrome (COWCK) is an X-linked recessive neuromuscular disorder characterized by early childhood onset of a slowly progressive axonal sensorimotor neuropathy associated in some patients with sensorineural deafness and cognitive impairment (summary by Rinaldi et al., 2012).
Clinical Description OMIM Cowchock et al. (1985) reported a large Italian American family with early childhood onset of a slowly progressive axonal sensorimotor neuropathy associated with deafness and cognitive impairment. The transmission pattern was consistent with X-linked recessive inheritance. Minor abnormalities ...
Molecular genetics OMIM By exome sequencing of 1 of the patients from the original family reported by Cowchock et al. (1985), Rinaldi et al. (2012) identified a hemizygous mutation in the AIFM1 gene (E493V; 300169.0002). The mutation was confirmed by Sanger ...