Charcot-Marie-Tooth Disease(s) Clinical CharacteristicsOcular Features: Optic atrophy is present in some patients, particularly in X-linked recessive (CMTX5; 311070), X-linked dominant (CMTX5; 302800), and autosomal recessive (CMT2A2B; 617087) disease. Congenital and juvenile-onset open-angle glaucoma has been reported among members of 2 consanguineous families with type 4B2, or CMT4B2; (604563). The mean age of onset was 8 years. Systemic Features: Charcot-Marie-Tooth disease is a large group of clinically and genetically heterogeneous disorders characterized by progressive motor and sensory polyneuropathy. These can be separated (with overlap) into two large groups on the basis of electrophysiologic criteria: type 1 is the demyelinating form, and type 2 the axonal form. Patients with primarily distal motor neuropathy are sometimes considered to comprise a third type. Symptoms such as weakness in the extremities and digits have a variable age of onset but usually become evident in late childhood or early adulthood. Small muscles of the hands and feet are often atrophied to some degree. Some patients develop hearing loss of the neurosensory type. Foot deformities such as pes cavus are common. Nerve conduction velocity (reduction) and electromyography can be helpful diagnostically. It may be helpful to look for characteristic changes such as loss of myelinated fibers and focal myelin sheath folding in sural nerve biopsies. Intellectual impairment and dementia are usually not features of Charcot-Marie-Tooth disease. Hemizygous individuals with X-linked types of CMT such as CMTX2-5 seem to be more likely to have intellectual disabilities, hearing loss, spasticity, and optic neuropathy. GeneticsCharcot-Marie-Tooth disease can also be classified on the basis of their hereditary patterns including autosomal dominant, autosomal recessive, X-linked recessive, and X-linked dominant. Each of these contains yet more distinct subtypes as defined by mutations in at least 40 genes. The wide range of disease severity and the overlapping of many signs can make pedigree construction and the determination of recurrence risks and prognosis challenging. The only recourse may be genotyping. See Charcot-Marie-Tooth Disease with Glaucoma (604563) for a form of this disease in which glaucoma occurs early. Pedigree: Autosomal dominantAutosomal recessiveX-linked dominant, father affectedX-linked dominant, mother affectedX-linked recessive, carrier motherX-linked recessive, father affectedTreatmentTreatment Options: The widespread and debilitating polyneuropathy requires a multidisciplinary management approach with neurologists, physical and occupational therapists, audiologists, pain specialists, and orthopedists. Pharmaceuticals such as gabapentin may be used for neuropathic pain. Surgery for pes cavus and joint dysplasias can be helpful. ReferencesArticle Title: Charcot-Marie-Tooth disease Carter GT, Weiss MD, Han JJ, Chance PF, England JD. Charcot-Marie-Tooth disease. Curr Treat Options Neurol. 2008 Mar;10(2):94-102. PubMed ID: 18334132 Mutations in MTMR13, a new pseudophosphatase homologue of MTMR2 and Sbf1, in two families with an autosomal recessive demyelinating form of Charcot-Marie-Tooth disease associated with early-onset glaucoma Azzedine H, Bolino A, Taieb T, Birouk N, Di Duca M, Bouhouche A, Benamou S, Mrabet A, Hammadouche T, Chkili T, Gouider R, Ravazzolo R, Brice A, Laporte J, LeGuern E. Mutations in MTMR13, a new pseudophosphatase homologue of MTMR2 and Sbf1, in two families with an autosomal recessive demyelinating form of Charcot-Marie-Tooth disease associated with early-onset glaucoma. Am J Hum Genet. 2003 May;72(5):1141-53. PubMed ID: 12687498 Hereditary motor and sensory neuropathy with myelin folding and juvenile onset glaucoma Kiwaki T, Umehara F, Takashima H, Nakagawa M, Kamimura K, Kashio N, Sakamoto Y, Unoki K, Nobuhara Y, Michizono K, Watanabe O, Arimura H, Osame M. Hereditary motor and sensory neuropathy with myelin folding and juvenile onset glaucoma. Neurology. 2000 Aug 8;55(3):392-7. PubMed ID: 10932274 Read more about Charcot-Marie-Tooth Disease(s)
Charcot-Marie-Tooth disease Carter GT, Weiss MD, Han JJ, Chance PF, England JD. Charcot-Marie-Tooth disease. Curr Treat Options Neurol. 2008 Mar;10(2):94-102. PubMed ID: 18334132
Mutations in MTMR13, a new pseudophosphatase homologue of MTMR2 and Sbf1, in two families with an autosomal recessive demyelinating form of Charcot-Marie-Tooth disease associated with early-onset glaucoma Azzedine H, Bolino A, Taieb T, Birouk N, Di Duca M, Bouhouche A, Benamou S, Mrabet A, Hammadouche T, Chkili T, Gouider R, Ravazzolo R, Brice A, Laporte J, LeGuern E. Mutations in MTMR13, a new pseudophosphatase homologue of MTMR2 and Sbf1, in two families with an autosomal recessive demyelinating form of Charcot-Marie-Tooth disease associated with early-onset glaucoma. Am J Hum Genet. 2003 May;72(5):1141-53. PubMed ID: 12687498
Hereditary motor and sensory neuropathy with myelin folding and juvenile onset glaucoma Kiwaki T, Umehara F, Takashima H, Nakagawa M, Kamimura K, Kashio N, Sakamoto Y, Unoki K, Nobuhara Y, Michizono K, Watanabe O, Arimura H, Osame M. Hereditary motor and sensory neuropathy with myelin folding and juvenile onset glaucoma. Neurology. 2000 Aug 8;55(3):392-7. PubMed ID: 10932274
