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Charcot-Marie-Tooth disease, type 2A(CMT2A)

MedGen UID:
389169
Concept ID:
C2079538
Disease or Syndrome
Synonyms: Charcot-Marie-Tooth disease, axonal, Type 2A; Charcot-Marie-Tooth disease, neuronal, Type 2A; Charcot-Marie-Tooth Neuropathy Type 2A; CMT2A; Hereditary motor and sensory neuropathy 2 A; HMSN IIA
 
Related genes: KIF1B, MFN2

Disease characteristics

Excerpted from the GeneReview: MFN2 Hereditary Motor and Sensory Neuropathy
MFN2 hereditary motor and sensory neuropathy (MFN2-HMSN) is a classic axonal peripheral sensorimotor neuropathy, inherited in either an autosomal dominant (AD) manner (~90%) or an autosomal recessive (AR) manner (~10%). MFN2-HMSN is characterized by more severe involvement of the lower extremities than the upper extremities, distal upper-extremity involvement as the neuropathy progresses, more prominent motor deficits than sensory deficits, and normal (>42 m/s) or only slightly decreased nerve conduction velocities (NCVs). Postural tremor is common. Median onset is age 12 years in the AD form and age eight years in the AR form. The prevalence of optic atrophy is approximately 7% in the AD form and approximately 20% in the AR form. [from GeneReviews]
Authors:
Stephan Züchner   view full author information

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Rizzo F, Bono S, Ruepp MD, Salani S, Ottoboni L, Abati E, Melzi V, Cordiglieri C, Pagliarani S, De Gioia R, Anastasia A, Taiana M, Garbellini M, Lodato S, Kunderfranco P, Cazzato D, Cartelli D, Lonati C, Bresolin N, Comi G, Nizzardo M, Corti S
Cell Mol Life Sci 2023 Nov 25;80(12):373. doi: 10.1007/s00018-023-05018-w. PMID: 38007410Free PMC Article
Zhang Y, Pang D, Wang Z, Ma L, Chen Y, Yang L, Xiao W, Yuan H, Chang F, Ouyang H
Gene 2023 Oct 20;883:147684. Epub 2023 Aug 1 doi: 10.1016/j.gene.2023.147684. PMID: 37536398

Recent clinical studies

Etiology

Franco A, Li J, Kelly DP, Hershberger RE, Marian AJ, Lewis RM, Song M, Dang X, Schmidt AD, Mathyer ME, Edwards JR, Strong CG, Dorn GW
Elife 2023 Nov 1;12 doi: 10.7554/eLife.84235. PMID: 37910431Free PMC Article
Hamedani AG, Wilson JA, Avery RA, Scherer SS
J Neuroophthalmol 2021 Jun 1;41(2):233-238. doi: 10.1097/WNO.0000000000000965. PMID: 32441898
Pipis M, Feely SME, Polke JM, Skorupinska M, Perez L, Shy RR, Laura M, Morrow JM, Moroni I, Pisciotta C, Taroni F, Vujovic D, Lloyd TE, Acsadi G, Yum SW, Lewis RA, Finkel RS, Herrmann DN, Day JW, Li J, Saporta M, Sadjadi R, Walk D, Burns J, Muntoni F, Ramchandren S, Horvath R, Johnson NE, Züchner S, Pareyson D, Scherer SS, Rossor AM, Shy ME, Reilly MM; Inherited Neuropathies Consortium - Rare Disease Clinical Research Network (INC-RDCRN)
Brain 2020 Dec 1;143(12):3589-3602. doi: 10.1093/brain/awaa323. PMID: 33415332Free PMC Article
Lv H, Wang L, Zhang W, Wang Z, Zuo Y, Liu J, Yuan Y
J Neurol Sci 2015 Nov 15;358(1-2):153-7. Epub 2015 Aug 28 doi: 10.1016/j.jns.2015.08.1528. PMID: 26382835
Engelfried K, Vorgerd M, Hagedorn M, Haas G, Gilles J, Epplen JT, Meins M
BMC Med Genet 2006 Jun 8;7:53. doi: 10.1186/1471-2350-7-53. PMID: 16762064Free PMC Article

Diagnosis

Franco A, Li J, Kelly DP, Hershberger RE, Marian AJ, Lewis RM, Song M, Dang X, Schmidt AD, Mathyer ME, Edwards JR, Strong CG, Dorn GW
Elife 2023 Nov 1;12 doi: 10.7554/eLife.84235. PMID: 37910431Free PMC Article
Dorn GW 2nd, Dang X
Cells 2022 Mar 19;11(6) doi: 10.3390/cells11061049. PMID: 35326500Free PMC Article
Hamedani AG, Wilson JA, Avery RA, Scherer SS
J Neuroophthalmol 2021 Jun 1;41(2):233-238. doi: 10.1097/WNO.0000000000000965. PMID: 32441898
Engelfried K, Vorgerd M, Hagedorn M, Haas G, Gilles J, Epplen JT, Meins M
BMC Med Genet 2006 Jun 8;7:53. doi: 10.1186/1471-2350-7-53. PMID: 16762064Free PMC Article
Santoro L, Manganelli F, Di Maio L, Barbieri F, Carella M, D'Adamo P, Casari G
Neuromuscul Disord 2002 May;12(4):399-404. doi: 10.1016/s0960-8966(01)00305-4. PMID: 12062259

Therapy

Shen S, Picci C, Ustinova K, Benoy V, Kutil Z, Zhang G, Tavares MT, Pavlíček J, Zimprich CA, Robers MB, Van Den Bosch L, Bařinka C, Langley B, Kozikowski AP
J Med Chem 2021 Apr 22;64(8):4810-4840. Epub 2021 Apr 8 doi: 10.1021/acs.jmedchem.0c02210. PMID: 33830764
Pipis M, Feely SME, Polke JM, Skorupinska M, Perez L, Shy RR, Laura M, Morrow JM, Moroni I, Pisciotta C, Taroni F, Vujovic D, Lloyd TE, Acsadi G, Yum SW, Lewis RA, Finkel RS, Herrmann DN, Day JW, Li J, Saporta M, Sadjadi R, Walk D, Burns J, Muntoni F, Ramchandren S, Horvath R, Johnson NE, Züchner S, Pareyson D, Scherer SS, Rossor AM, Shy ME, Reilly MM; Inherited Neuropathies Consortium - Rare Disease Clinical Research Network (INC-RDCRN)
Brain 2020 Dec 1;143(12):3589-3602. doi: 10.1093/brain/awaa323. PMID: 33415332Free PMC Article
De Gioia R, Citterio G, Abati E, Nizzardo M, Bresolin N, Comi GP, Corti S, Rizzo F
Mol Neurobiol 2020 Dec;57(12):5121-5129. Epub 2020 Aug 27 doi: 10.1007/s12035-020-02081-3. PMID: 32856204Free PMC Article
Rocha AG, Franco A, Krezel AM, Rumsey JM, Alberti JM, Knight WC, Biris N, Zacharioudakis E, Janetka JW, Baloh RH, Kitsis RN, Mochly-Rosen D, Townsend RR, Gavathiotis E, Dorn GW 2nd
Science 2018 Apr 20;360(6386):336-341. doi: 10.1126/science.aao1785. PMID: 29674596Free PMC Article

Prognosis

Dorn GW 2nd, Dang X
Cells 2022 Mar 19;11(6) doi: 10.3390/cells11061049. PMID: 35326500Free PMC Article
Pipis M, Feely SME, Polke JM, Skorupinska M, Perez L, Shy RR, Laura M, Morrow JM, Moroni I, Pisciotta C, Taroni F, Vujovic D, Lloyd TE, Acsadi G, Yum SW, Lewis RA, Finkel RS, Herrmann DN, Day JW, Li J, Saporta M, Sadjadi R, Walk D, Burns J, Muntoni F, Ramchandren S, Horvath R, Johnson NE, Züchner S, Pareyson D, Scherer SS, Rossor AM, Shy ME, Reilly MM; Inherited Neuropathies Consortium - Rare Disease Clinical Research Network (INC-RDCRN)
Brain 2020 Dec 1;143(12):3589-3602. doi: 10.1093/brain/awaa323. PMID: 33415332Free PMC Article
Barbullushi K, Abati E, Rizzo F, Bresolin N, Comi GP, Corti S
Mol Neurobiol 2019 Sep;56(9):6460-6471. Epub 2019 Mar 4 doi: 10.1007/s12035-019-1533-2. PMID: 30830587
Lv H, Wang L, Zhang W, Wang Z, Zuo Y, Liu J, Yuan Y
J Neurol Sci 2015 Nov 15;358(1-2):153-7. Epub 2015 Aug 28 doi: 10.1016/j.jns.2015.08.1528. PMID: 26382835
Bombelli F, Stojkovic T, Dubourg O, Echaniz-Laguna A, Tardieu S, Larcher K, Amati-Bonneau P, Latour P, Vignal O, Cazeneuve C, Brice A, Leguern E
JAMA Neurol 2014 Aug;71(8):1036-42. doi: 10.1001/jamaneurol.2014.629. PMID: 24957169

Clinical prediction guides

Abati E, Manini A, Velardo D, Del Bo R, Napoli L, Rizzo F, Moggio M, Bresolin N, Bellone E, Bassi MT, D'Angelo MG, Comi GP, Corti S
Sci Rep 2022 Apr 13;12(1):6181. doi: 10.1038/s41598-022-10220-0. PMID: 35418194Free PMC Article
Dorn GW 2nd, Dang X
Cells 2022 Mar 19;11(6) doi: 10.3390/cells11061049. PMID: 35326500Free PMC Article
Pipis M, Feely SME, Polke JM, Skorupinska M, Perez L, Shy RR, Laura M, Morrow JM, Moroni I, Pisciotta C, Taroni F, Vujovic D, Lloyd TE, Acsadi G, Yum SW, Lewis RA, Finkel RS, Herrmann DN, Day JW, Li J, Saporta M, Sadjadi R, Walk D, Burns J, Muntoni F, Ramchandren S, Horvath R, Johnson NE, Züchner S, Pareyson D, Scherer SS, Rossor AM, Shy ME, Reilly MM; Inherited Neuropathies Consortium - Rare Disease Clinical Research Network (INC-RDCRN)
Brain 2020 Dec 1;143(12):3589-3602. doi: 10.1093/brain/awaa323. PMID: 33415332Free PMC Article
Beręsewicz M, Charzewski Ł, Krzyśko KA, Kochański A, Zabłocka B
Sci Rep 2018 Nov 15;8(1):16900. doi: 10.1038/s41598-018-35133-9. PMID: 30442897Free PMC Article
Bombelli F, Stojkovic T, Dubourg O, Echaniz-Laguna A, Tardieu S, Larcher K, Amati-Bonneau P, Latour P, Vignal O, Cazeneuve C, Brice A, Leguern E
JAMA Neurol 2014 Aug;71(8):1036-42. doi: 10.1001/jamaneurol.2014.629. PMID: 24957169

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