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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): 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.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
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.
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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.
See: Feature record | Search on this feature
Hand muscle atrophy
MedGen UID:
116091
•Concept ID:
C0239830
•
Finding
Muscular atrophy involving the muscles of the hand.
See: Feature record | Search on this feature
Distal muscle weakness
MedGen UID:
140883
•Concept ID:
C0427065
•
Finding
Reduced strength of the musculature of the distal extremities.
See: Feature record | Search on this feature
Distal amyotrophy
MedGen UID:
338530
•Concept ID:
C1848736
•
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCharcot-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: 31356216Free 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

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

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

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

Supplemental Content