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Charcot-Marie-Tooth disease axonal type 2U(CMT2U)

MedGen UID:: 906504
•Concept ID:: C4084821
•: Disease or Syndrome

Synonyms:	CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2U; CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2U
SNOMED CT:	Autosomal dominant Charcot-Marie-Tooth disease type 2 due to MARS mutation (765046002); Autosomal dominant Charcot-Marie-Tooth disease type 2U (765046002); Autosomal dominant Charcot-Marie-Tooth disease type 2 due to MARS (methionyl-tRNA synthetase) mutation (765046002)
Modes of inheritance:	Autosomal dominant inheritance MedGen UID: 141047 •Concept ID: C0443147 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Autosomal dominant inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	MARS1 (12q13.3)

Monarch Initiative:	MONDO:0014566
OMIM®:	616280
Orphanet:	ORPHA397735

Definition

Charcot-Marie-Tooth disease type 2U (CMT2U) is an autosomal dominant neurologic disorder characterized by late-adult onset of distal sensory impairment resulting in distal muscle weakness and atrophy affecting the upper and lower limbs. The disorder is slowly progressive (summary by Gonzalez et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210). [from OMIM]

Clinical features

From HPO

Hand muscle weakness

MedGen UID:: 66798
•Concept ID:: C0239831
•: Finding

Reduced strength of the musculature of the hand.

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Foot dorsiflexor weakness

MedGen UID:: 356163
•Concept ID:: C1866141
•: Finding

Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.

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Areflexia

MedGen UID:: 115943
•Concept ID:: C0234146
•: Finding

Absence of neurologic reflexes such as the knee-jerk reaction.

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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.

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Gait disturbance

MedGen UID:: 107895
•Concept ID:: C0575081
•: Finding

The term gait disturbance can refer to any disruption of the ability to walk. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.

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Peripheral axonal neuropathy

MedGen UID:: 266071
•Concept ID:: C1263857
•: Disease or Syndrome

An abnormality characterized by disruption of the normal functioning of peripheral axons.

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Distal sensory impairment

MedGen UID:: 335722
•Concept ID:: C1847584
•: Finding

An abnormal reduction in sensation in the distal portions of the extremities.

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Hand muscle atrophy

MedGen UID:: 116091
•Concept ID:: C0239830
•: Finding

Muscular atrophy involving the muscles of the hand.

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Difficulty walking

MedGen UID:: 86319
•Concept ID:: C0311394
•: Finding

Reduced ability to walk (ambulate).

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Distal muscle weakness

MedGen UID:: 140883
•Concept ID:: C0427065
•: Finding

Reduced strength of the musculature of the distal extremities.

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Distal amyotrophy

MedGen UID:: 338530
•Concept ID:: C1848736
•: Disease or Syndrome

Muscular atrophy affecting muscles in the distal portions of the extremities.

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Abnormality of limbs
- Foot dorsiflexor weakness
- Hand muscle weakness
Abnormality of the musculoskeletal system
Abnormality of the nervous system

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVCharcot-Marie-Tooth disease axonal type 2U

Fetal anomaly
- Congenital Systemic Disorder
  - Abnormality of the nervous system
    - Hereditary motor and sensory neuropathy
      - Charcot-Marie-Tooth disease
        Charcot-Marie-Tooth disease type 2
        Charcot-Marie-Tooth disease axonal type 2U

Recent clinical studies

Etiology

A Novel Mutation in MARS in a Patient with Charcot-Marie-Tooth Disease, Axonal, Type 2U with Congenital Onset.

Gillespie MK, McMillan HJ, Kernohan KD, Pena IA, Meyer-Schuman R; Care4Rare Canada Consortium, Antonellis A, Boycott KM
J Neuromuscul Dis 2019;6(3):333-339. doi: 10.3233/JND-190404. PMID: 31356216 Free PMC Article

Whole-exome sequencing reveals a novel missense mutation in the MARS gene related to a rare Charcot-Marie-Tooth neuropathy type 2U.

Sagi-Dain L, Shemer L, Zelnik N, Zoabi Y, Orit S, Adir V, Schif A, Peleg A
J Peripher Nerv Syst 2018 Jun;23(2):138-142. Epub 2018 May 9 doi: 10.1111/jns.12264. PMID: 29582526

See all (2)

Diagnosis

Clinicopathological features in two families with MARS-related Charcot-Marie-Tooth disease.

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

Whole-exome sequencing reveals a novel missense mutation in the MARS gene related to a rare Charcot-Marie-Tooth neuropathy type 2U.

Sagi-Dain L, Shemer L, Zelnik N, Zoabi Y, Orit S, Adir V, Schif A, Peleg A
J Peripher Nerv Syst 2018 Jun;23(2):138-142. Epub 2018 May 9 doi: 10.1111/jns.12264. PMID: 29582526

Mutations in methionyl-tRNA synthetase gene in a Chinese family with interstitial lung and liver disease, postnatal growth failure and anemia.

Sun Y, Hu G, Luo J, Fang D, Yu Y, Wang X, Chen J, Qiu W
J Hum Genet 2017 Jun;62(6):647-651. Epub 2017 Feb 2 doi: 10.1038/jhg.2017.10. PMID: 28148924

See all (3)

Prognosis

Whole-exome sequencing reveals a novel missense mutation in the MARS gene related to a rare Charcot-Marie-Tooth neuropathy type 2U.

Sagi-Dain L, Shemer L, Zelnik N, Zoabi Y, Orit S, Adir V, Schif A, Peleg A
J Peripher Nerv Syst 2018 Jun;23(2):138-142. Epub 2018 May 9 doi: 10.1111/jns.12264. PMID: 29582526

See all (1)

Clinical prediction guides

Whole-exome sequencing reveals a novel missense mutation in the MARS gene related to a rare Charcot-Marie-Tooth neuropathy type 2U.

Sagi-Dain L, Shemer L, Zelnik N, Zoabi Y, Orit S, Adir V, Schif A, Peleg A
J Peripher Nerv Syst 2018 Jun;23(2):138-142. Epub 2018 May 9 doi: 10.1111/jns.12264. PMID: 29582526

See all (1)

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Charcot-Marie-Tooth disease axonal type 2U(CMT2U)

Definition

Clinical features

Term Hierarchy

Recent clinical studies

Etiology

Diagnosis

Prognosis

Clinical prediction guides

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Molecular resources

Consumer resources

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