Skip to
  1. Homepage
  2. Rare diseases
  3. Search
Simple search

Simple search

(*) mandatory field


Other search option(s)

X-linked Charcot-Marie-Tooth disease

Synonym(s) CMTX
X-linked hereditary motor and sensory neuropathy
Prevalence 1-9 / 100 000
Inheritance X-linked recessive
or X-linked dominant
Age of onset -
  • G60.0
MeSH -
MedDRA -


Disease definition

X-linked Charcot-Marie-Tooth disease (CMTX) belongs to the genetically heterogeneous group of CMT peripheral sensorimotor polyneuropathy diseases.

Clinical description

CMTX1 is characterized by a slowly progressive course: muscle wasting and weakness of distal limb muscles mainly involving the feet, legs and hands (particularly the thenar eminence), with proximal muscle weakness occurring in severe cases; distal sensory loss; loss of deep tendon reflexes; pes cavus and more rarely scoliosis. Rare instances of transient central nervous system (CNS) dysfunction have been described, with dysarthria, dysphagia, weakness, ataxia, and even aphasia and somnolence. All forms of CMTX are rare and are characterized by intellectual deficit (CMTX2, CMTX4), spastic paraplegia (CMTX3), hearing loss (CMTX4, CMTX5, rarely CMTX1), and optic atrophy (CMTX5).


CMTX1 is associated with mutations in the GJB1 gene (Xq13.1), encoding connexin 32 (Cx32). Cx32 forms gap-junctions in non-compact myelin produced by myelinating Schwann cells. Cx32 is also expressed in oligodendrocytes, explaining the potential CNS involvement. CMTX5 is associated with mutations in the phosphoribosylpyrophosphate synthetase 1 gene (PRPS1). CMTX1 is transmitted as an X-linked dominant trait and males are more severely affected than females, whereas the other CMTX types are X-linked recessive and female carriers are usually unaffected.

Diagnostic methods

Diagnosis is based on family and personal history, clinical examination, nerve conduction studies (NCS), and DNA testing (for CMTX1). NCS show a sensorimotor polyneuropathy with decreased conduction velocities in males (usually in the intermediate range of 30-45 m/s in upper limb motor nerves) and mildly decreased or even normal velocities in females. In contrast with other CMT types, conduction slowing is frequently nonhomogeneous, with temporal dispersion and sometimes conduction blocks, and the median nerve being more severely affected than the ulnar nerve. Nerve biopsy reveals prominent axonal changes, in spite of nerve conduction slowing, with evidence of ultrastructural abnormalities in the paranodal regions. Auditory evoked potentials usually reveal abnormalities of central waves in the brainstem, consistent with frequent subclinical brain involvement in CMTX1.

Differential diagnosis

Differential diagnosis includes other CMT types and acquired dysimmune neuropathies such as chronic inflammatory demyelinating polyradiculoneuropathy (see these terms).

Antenatal diagnosis

Prenatal diagnosis is possible for CMTX1 when the mutation is known.

Genetic counseling

As an X-linked dominant trait, there is no male-to-male transmission; female carriers are usually mildly affected and have a 50% risk of transmitting the disease to their offspring.

Management and treatment

There is no drug treatment available. Rehabilitation therapy and surgical treatment of skeletal deformities are the only options.


CMTX1 is moderately severe for affected males, who may loose ambulation capacity later in life.

Expert reviewer(s)

  • Dr Davide PAREYSON

(*) Required fields.

Attention: Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed.

Captcha image

Detailed information

Anesthesia guidelines
Clinical practice guidelines
Guidance for genetic testing
Article for general public
Get Acrobat Reader
The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.