X-Linked Charcot-Marie-Tooth Disease (CMTX)

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UMLS 73 C0393808

NIH Rare Diseases : ⁵³ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 64747Disease definitionX-linked Charcot-Marie-Tooth disease (CMTX) belongs to the genetically heterogeneous group of CMT peripheral sensorimotor polyneuropathy diseases.Clinical descriptionCMTX1 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).EtiologyCMTX1 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 dominanttrait and males are more severely affected than females, whereas the other CMTX types are X-linked recessive and female carriers are usually unaffected.Diagnostic methodsDiagnosis 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 diagnosisDifferential diagnosis includes other CMT types and acquired dysimmune neuropathies such as chronic inflammatory demyelinating polyradiculoneuropathy (see these terms).Antenatal diagnosisPrenatal diagnosis is possible for CMTX1 when the mutation is known.Genetic counselingAs 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 treatmentThere is no drug treatment available. Rehabilitation therapy and surgical treatment of skeletal deformities are the only options.PrognosisCMTX1 is moderately severe for affected males, who may loose ambulation capacity later in life.Visit the Orphanet disease page for more resources.

MalaCards based summary : X-Linked Charcot-Marie-Tooth Disease, also known as x-linked hereditary motor and sensory neuropathy, is related to charcot-marie-tooth disease, x-linked recessive, 5 and charcot-marie-tooth disease, x-linked recessive, 3, and has symptoms including tremor, paraparesis and numbness. An important gene associated with X-Linked Charcot-Marie-Tooth Disease is GJB1 (Gap Junction Protein Beta 1), and among its related pathways/superpathways are Gap junction trafficking and Transport of connexins along the secretory pathway. Affiliated tissues include brain, testes and eye, and related phenotypes are Decreased viability and Decreased viability

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Decreased viability	GR00055-A-2	8.92	GJB1 PDK3
2	Decreased viability	GR00402-S-2	8.92	GJB1 PDK3

Search Clinical Trials , NIH Clinical Center for X-Linked Charcot-Marie-Tooth Disease

Search GEO for disease gene expression data for X-Linked Charcot-Marie-Tooth Disease.