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Charcot-Marie-Tooth disease, dominant intermediate A(CMTDIA)

MedGen UID:
376235
Concept ID:
C1847896
Disease or Syndrome
Synonyms: CHARCOT-MARIE-TOOTH NEUROPATHY, DOMINANT INTERMEDIATE A; CMTDIA
SNOMED CT: Autosomal dominant intermediate Charcot-Marie-Tooth disease type A (765744006)
 
Monarch Initiative: MONDO:0957273
OMIM®: 620378

Definition

Charcot-Marie-Tooth disease, dominant intermediate-A (CMTDIA) is an autosomal dominant peripheral neuropathy characterized by onset of symptoms in the first or second decades of life. Affected individuals have difficulty walking with muscle cramps of the lower limbs; the motor symptoms may be worsened by cold. The disorder is slowly progressive, eventually involving all 4 limbs, but patients remain ambulatory. After age 40, patients develop more severe features, including distal muscle weakness and atrophy, pes cavus, areflexia, and distal sensory loss. Electrophysiologic studies yield nerve conduction velocities with 'intermediate' values between demyelinating and axonal neuropathy (see below). One such family has been reported (Rossi et al., 1985). [from OMIM]

Clinical features

From HPO
Limb muscle weakness
MedGen UID:
107956
Concept ID:
C0587246
Finding
Reduced strength and weakness of the muscles of the arms and legs.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Steppage gait
MedGen UID:
98105
Concept ID:
C0427149
Finding
An abnormal gait pattern that arises from weakness of the pretibial and peroneal muscles due to a lower motor neuron lesion. Affected patients have footdrop and are unable to dorsiflex and evert the foot. The leg is lifted high on walking so that the toes clear the ground, and there may be a slapping noise when the foot strikes the ground again.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Peripheral demyelination
MedGen UID:
451074
Concept ID:
C0878575
Pathologic Function
A loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system.
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
Onion bulb formation
MedGen UID:
376237
Concept ID:
C1847906
Finding
Repeated episodes of segmental demyelination and remyelination lead to the accumulation of supernumerary Schwann cells around axons, which is referred to as onion bulb formation. This finding affects peripheral nerves.
Axonal degeneration/regeneration
MedGen UID:
368889
Concept ID:
C1968790
Finding
A pattern of simultaneous degeneration and regeneration of axons (see comment).
Somatic sensory dysfunction
MedGen UID:
1790456
Concept ID:
C5551413
Finding
An abnormality of the primary sensation that is mediated by peripheral nerves (pain, temperature, touch, vibration, joint position). The word hypoesthesia (or hypesthesia) refers to a reduction in cutaneous sensation to a specific type of testing.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).

Professional guidelines

PubMed

Bansagi B, Antoniadi T, Burton-Jones S, Murphy SM, McHugh J, Alexander M, Wells R, Davies J, Hilton-Jones D, Lochmüller H, Chinnery P, Horvath R
J Neurol 2015 Aug;262(8):1899-908. Epub 2015 Jun 2 doi: 10.1007/s00415-015-7778-4. PMID: 26032230Free PMC Article

Recent clinical studies

Etiology

Espinós C, Calpena E, Martínez-Rubio D, Lupo V
Adv Exp Med Biol 2012;724:61-75. doi: 10.1007/978-1-4614-0653-2_5. PMID: 22411234
Yiu EM, Geevasinga N, Nicholson GA, Fagan ER, Ryan MM, Ouvrier RA
Neurology 2011 Feb 1;76(5):461-6. doi: 10.1212/WNL.0b013e31820a0ceb. PMID: 21282593
Nicholson G, Myers S
Neuromolecular Med 2006;8(1-2):123-30. doi: 10.1385/nmm:8:1-2:123. PMID: 16775371
Houlden H, Reilly MM
Neuromolecular Med 2006;8(1-2):43-62. doi: 10.1385/nmm:8:1-2:43. PMID: 16775366
Pareyson D, Scaioli V, Laurà M
Neuromolecular Med 2006;8(1-2):3-22. doi: 10.1385/nmm:8:1-2:3. PMID: 16775364

Diagnosis

Ma Z, Lv H, Zhang H, Wang H, Li J, Yu M, Zhu Y, Huang D, Meng L, Yuan Y
Neuropathology 2022 Dec;42(6):505-511. Epub 2022 Jun 20 doi: 10.1111/neup.12842. PMID: 35723632
Sun SC, Ma D, Li MY, Zhang RX, Huang C, Huang HJ, Xie YZ, Wang ZJ, Liu J, Cai DC, Liu CX, Yang Q, Bao FX, Gong XL, Li JR, Hui Z, Wei XF, Zhong JM, Zhou WJ, Shang X, Zhang C, Liu XG, Tang BS, Xiong F, Xu XM
Brain 2019 Aug 1;142(8):2215-2229. doi: 10.1093/brain/awz151. PMID: 31199454
Liu L, Zhang R
Neurosci Bull 2014 Dec;30(6):999-1009. Epub 2014 Oct 17 doi: 10.1007/s12264-014-1475-7. PMID: 25326399Free PMC Article
Yiu EM, Geevasinga N, Nicholson GA, Fagan ER, Ryan MM, Ouvrier RA
Neurology 2011 Feb 1;76(5):461-6. doi: 10.1212/WNL.0b013e31820a0ceb. PMID: 21282593
Nicholson G, Myers S
Neuromolecular Med 2006;8(1-2):123-30. doi: 10.1385/nmm:8:1-2:123. PMID: 16775371

Prognosis

San Luis CV, Schwartzlow C, Nozaki K, Ubogu EE
J Investig Med High Impact Case Rep 2022 Jan-Dec;10:23247096221117801. doi: 10.1177/23247096221117801. PMID: 35993408Free PMC Article
Thomas FP, Guergueltcheva V, Gondim FA, Tournev I, Rao CV, Ishpekova B, Kinsella LJ, Pan Y, Geller TJ, Litvinenko I, De Jonghe P, Scherer SS, Jordanova A
J Neurol 2016 Mar;263(3):467-76. Epub 2016 Jan 2 doi: 10.1007/s00415-015-7989-8. PMID: 26725087
Berciano J, García A, Peeters K, Gallardo E, De Vriendt E, Pelayo-Negro AL, Infante J, Jordanova A
J Neurol 2015 May;262(5):1289-300. Epub 2015 Apr 1 doi: 10.1007/s00415-015-7709-4. PMID: 25877835
Nicolaou P, Cianchetti C, Minaidou A, Marrosu G, Zamba-Papanicolaou E, Middleton L, Christodoulou K
Eur J Hum Genet 2013 Feb;21(2):190-4. Epub 2012 Jul 11 doi: 10.1038/ejhg.2012.146. PMID: 22781092Free PMC Article
Pareyson D, Scaioli V, Laurà M
Neuromolecular Med 2006;8(1-2):3-22. doi: 10.1385/nmm:8:1-2:3. PMID: 16775364

Clinical prediction guides

San Luis CV, Schwartzlow C, Nozaki K, Ubogu EE
J Investig Med High Impact Case Rep 2022 Jan-Dec;10:23247096221117801. doi: 10.1177/23247096221117801. PMID: 35993408Free PMC Article
Hines TJ, Tadenev ALD, Lone MA, Hatton CL, Bagasrawala I, Stum MG, Miers KE, Hornemann T, Burgess RW
J Anat 2022 Nov;241(5):1169-1185. Epub 2021 Dec 7 doi: 10.1111/joa.13605. PMID: 34875719Free PMC Article
Figueiredo FB, Silva WA Jr, Giuliatti S, Tomaselli PJ, Lourenço CM, Gouvêa SP, Covaleski APPM, Hallak JE, Marques W Jr
Neuromuscul Disord 2021 Jun;31(6):505-511. Epub 2021 Mar 20 doi: 10.1016/j.nmd.2021.03.005. PMID: 33903021
Mathis S, Funalot B, Boyer O, Lacroix C, Marcorelles P, Magy L, Richard L, Antignac C, Vallat JM
J Neuropathol Exp Neurol 2014 Mar;73(3):223-33. doi: 10.1097/NEN.0000000000000047. PMID: 24487800
Froelich CA, First EA
Biochemistry 2011 Aug 23;50(33):7132-45. Epub 2011 Jul 26 doi: 10.1021/bi200989h. PMID: 21732632

Recent systematic reviews

Berciano J, García A, Gallardo E, Peeters K, Pelayo-Negro AL, Álvarez-Paradelo S, Gazulla J, Martínez-Tames M, Infante J, Jordanova A
J Neurol 2017 Aug;264(8):1655-1677. Epub 2017 Mar 31 doi: 10.1007/s00415-017-8474-3. PMID: 28364294

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