Charcot-Marie-Tooth (CMT) disease, also called hereditary motor and sensory neuropathy (HMSN), is a group of disorders characterized by a chronic motor and sensory polyneuropathy. Based on nerve conduction velocities, the disease can be divided into demyelinating CMT (CMT1), axonal CMT (CMT2) and intermediate CMT (CMTDI/CMTRI). Although more than 70 disease genes for CMT are known, a large number of affected individuals remain without a genetic diagnosis.
Category
Neurodegenerative disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
Disorders of nerve root, plexus or peripheral nerves
Hereditary neuropathy
8C20 Hereditary motor and sensory neuropathy
H00264 Charcot-Marie-Tooth disease
Pathway-based classification of diseases [BR:br08402]
Replication and repair
nt06509 DNA replication
H00264 Charcot-Marie-Tooth disease
Signal transduction
nt06528 Calcium signaling
H00264 Charcot-Marie-Tooth disease
Cellular process
nt06515 Regulation of kinetochore-microtubule interactions
H00264 Charcot-Marie-Tooth disease
nt06532 Autophagy
H00264 Charcot-Marie-Tooth disease
nt06536 Mitophagy
H00264 Charcot-Marie-Tooth disease
nt06539 Cytoskeleton in muscle cells
H00264 Charcot-Marie-Tooth disease
nt06541 Cytoskeleton in neurons
H00264 Charcot-Marie-Tooth disease
nt06544 Neuroactive ligand signaling
H00264 Charcot-Marie-Tooth disease
nt06546 IgSF CAM signaling
H00264 Charcot-Marie-Tooth disease
CMT1: Abnormal myelin, autosomal dominant
CMT2: Axonopathy, autosomal dominant
Intermediate form: Combination of myelinopathy and axonopathy in individual, autosomal dominant
CMT4: Either myelinopathy or axonopathy, autosomal recessive
CMTX: Axonopathy with secondary myelin changes, X-linked dominant
MNMN: Mononeuropathy of the median nerve mild
Rebelo AP, Cortese A, Abraham A, Eshed-Eisenbach Y, Shner G, Vainshtein A, Buglo E, Camarena V, Gaidosh G, Shiekhattar R, Abreu L, Courel S, Burns DK, Bai Y, Bacon C, Feely SME, Castro D, Peles E, Reilly MM, Shy ME, Zuchner S
Title
A CADM3 variant causes Charcot-Marie-Tooth disease with marked upper limb involvement.
Guernsey DL, Jiang H, Bedard K, Evans SC, Ferguson M, Matsuoka M, Macgillivray C, Nightingale M, Perry S, Rideout AL, Orr A, Ludman M, Skidmore DL, Benstead T, Samuels ME
Title
Mutation in the gene encoding ubiquitin ligase LRSAM1 in patients with Charcot-Marie-Tooth disease.
Cottenie E, Kochanski A, Jordanova A, Bansagi B, Zimon M, Horga A, Jaunmuktane Z, Saveri P, Rasic VM, Baets J, Bartsakoulia M, Ploski R, Teterycz P, Nikolic M, Quinlivan R, Laura M, Sweeney MG, Taroni F, Lunn MP, Moroni I, Gonzalez M, Hanna MG, Bettencourt C, Chabrol E, Franke A, von Au K, Schilhabel M, Kabzinska D, Hausmanowa-Petrusewicz I, Brandner S, Lim SC, Song H, Choi BO, Horvath R, Chung KW, Zuchner S, Pareyson D, Harms M, Reilly MM, Houlden H
Title
Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2.
Higuchi Y, Hashiguchi A, Yuan J, Yoshimura A, Mitsui J, Ishiura H, Tanaka M, Ishihara S, Tanabe H, Nozuma S, Okamoto Y, Matsuura E, Ohkubo R, Inamizu S, Shiraishi W, Yamasaki R, Ohyagi Y, Kira J, Oya Y, Yabe H, Nishikawa N, Tobisawa S, Matsuda N, Masuda M, Kugimoto C, Fukushima K, Yano S, Yoshimura J, Doi K, Nakagawa M, Morishita S, Tsuji S, Takashima H
Title
Mutations in MME cause an autosomal-recessive Charcot-Marie-Tooth disease type 2.
Delague V, Jacquier A, Hamadouche T, Poitelon Y, Baudot C, Boccaccio I, Chouery E, Chaouch M, Kassouri N, Jabbour R, Grid D, Megarbane A, Haase G, Levy N
Title
Mutations in FGD4 encoding the Rho GDP/GTP exchange factor FRABIN cause autosomal recessive Charcot-Marie-Tooth type 4H.
Chelban V, Wilson MP, Warman Chardon J, Vandrovcova J, Zanetti MN, Zamba-Papanicolaou E, Efthymiou S, Pope S, Conte MR, Abis G, Liu YT, Tribollet E, Haridy NA, Botia JA, Ryten M, Nicolaou P, Minaidou A, Christodoulou K, Kernohan KD, Eaton A, Osmond M, Ito Y, Bourque P, Jepson JEC, Bello O, Bremner F, Cordivari C, Reilly MM, Foiani M, Heslegrave A, Zetterberg H, Heales SJR, Wood NW, Rothman JE, Boycott KM, Mills PB, Clayton PT, Houlden H
Title
PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation.
Kennerson ML, Yiu EM, Chuang DT, Kidambi A, Tso SC, Ly C, Chaudhry R, Drew AP, Rance G, Delatycki MB, Zuchner S, Ryan MM, Nicholson GA
Title
A new locus for X-linked dominant Charcot-Marie-Tooth disease (CMTX6) is caused by mutations in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene.
Azzedine H, Zavadakova P, Plante-Bordeneuve V, Vaz Pato M, Pinto N, Bartesaghi L, Zenker J, Poirot O, Bernard-Marissal N, Arnaud Gouttenoire E, Cartoni R, Title A, Venturini G, Medard JJ, Makowski E, Schols L, Claeys KG, Stendel C, Roos A, Weis J, Dubourg O, Leal Loureiro J, Stevanin G, Said G, Amato A, Baraban J, LeGuern E, Senderek J, Rivolta C, Chrast R
Title
PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease.
Tamiya G, Makino S, Hayashi M, Abe A, Numakura C, Ueki M, Tanaka A, Ito C, Toshimori K, Ogawa N, Terashima T, Maegawa H, Yanagisawa D, Tooyama I, Tada M, Onodera O, Hayasaka K
Title
A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-Marie-Tooth disease.
Auer-Grumbach M, Weger M, Fink-Puches R, Papic L, Frohlich E, Auer-Grumbach P, El Shabrawi-Caelen L, Schabhuttl M, Windpassinger C, Senderek J, Budka H, Trajanoski S, Janecke AR, Haas A, Metze D, Pieber TR, Guelly C
Title
Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin.
Djordjevic D, Pinard M, Gauthier MS, Smith-Hicks C, Hoffman TL, Wolf NI, Oegema R, van Binsbergen E, Baskin B, Bernard G, Fribourg S, Coulombe B, Yoon G
Title
De novo variants in POLR3B cause ataxia, spasticity, and demyelinating neuropathy.
Montecchiani C, Pedace L, Lo Giudice T, Casella A, Mearini M, Gaudiello F, Pedroso JL, Terracciano C, Caltagirone C, Massa R, St George-Hyslop PH, Barsottini OG, Kawarai T, Orlacchio A
Title
ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease.
Roussy-Levy syndrome (RLS) is a dominantly inherited early-onset syndrome consisting of gait ataxia, pes cavus, areflexia, eventually associated with muscle atrophy, postural tremors, limb ataxia, kyphoscoliosis, and sensory loss. The RLS subtype is not genetically homogeneous. RLS has been described as a phenotypic variant of Charcot-Marie-Tooth disease [DS:H00264] type 1A (CMT-1A) associated with duplications of the PMP22 gene. A mutations in the MPZ gene has been revealed indicating that the original RLS may fall under the CMT-1B subgroup of hereditary demyelinating neuropathies.
Category
Nervous system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
Disorders of nerve root, plexus or peripheral nerves
Hereditary neuropathy
8C20 Hereditary motor and sensory neuropathy
H01155 Roussy-Levy syndrome
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06546 IgSF CAM signaling
H01155 Roussy-Levy syndrome
Congenital hypomyelinating neuropathy (CHN) is a rare congenital neuropathy, often accompanied by arthrogryposis, that is characterized by prenatal onset, areflexia, hypotonia, hypomyelination, and slowed nerve conduction velocities. Previous reports of genetic analyses of patients have described mutations in genes known to be important in myelination.
Category
Nervous system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
Disorders of nerve root, plexus or peripheral nerves
Hereditary neuropathy
8C20 Hereditary motor and sensory neuropathy
H02357 Congenital hypomyelinating neuropathy
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06546 IgSF CAM signaling
H02357 Congenital hypomyelinating neuropathy
Funalot B, Topilko P, Arroyo MA, Sefiani A, Hedley-Whyte ET, Yoldi ME, Richard L, Touraille E, Laurichesse M, Khalifa E, Chauzeix J, Ouedraogo A, Cros D, Magdelaine C, Sturtz FG, Urtizberea JA, Charnay P, Bragado FG, Vallat JM
Title
Homozygous deletion of an EGR2 enhancer in congenital amyelinating neuropathy.
Dejerine-Sottas disease (DSD), also known as Charcot-Marie-Tooth disease type 3, is a severe, demyelinating neuropathy, presenting in infancy with delayed motor development, very slow nerve conduction velocities and elevated CSF protein. Progression is severe and walking ability is lost early. Hypomyelination and classic onion bulbs are the pathological hallmarks. Mutations in MPZ, PMP22, EGR2, and PRX are the most common causes of DSD. In more than 50% of cases, a causative genetic mutation cannot be identified.
Category
Nervous system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
Disorders of nerve root, plexus or peripheral nerves
Hereditary neuropathy
8C20 Hereditary motor and sensory neuropathy
H02359 Dejerine-Sottas disease
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06546 IgSF CAM signaling
H02359 Dejerine-Sottas disease
Baets J, Deconinck T, De Vriendt E, Zimon M, Yperzeele L, Van Hoorenbeeck K, Peeters K, Spiegel R, Parman Y, Ceulemans B, Van Bogaert P, Pou-Serradell A, Bernert G, Dinopoulos A, Auer-Grumbach M, Sallinen SL, Fabrizi GM, Pauly F, Van den Bergh P, Bilir B, Battaloglu E, Madrid RE, Kabzinska D, Kochanski A, Topaloglu H, Miller G, Jordanova A, Timmerman V, De Jonghe P
Title
Genetic spectrum of hereditary neuropathies with onset in the first year of life.
