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Charcot-Marie-Tooth disease dominant intermediate C(CMTDIC)

MedGen UID:
334023
Concept ID:
C1842237
Disease or Syndrome
Synonyms: CHARCOT-MARIE-TOOTH NEUROPATHY, DOMINANT INTERMEDIATE C; CMTDIC
SNOMED CT: Autosomal dominant intermediate Charcot-Marie-Tooth disease type C (765746008)
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.
 
Gene (location): YARS1 (1p35.1)
 
Monarch Initiative: MONDO:0012012
OMIM®: 608323
Orphanet: ORPHA100045

Definition

A rare hereditary motor and sensory neuropathy characterized by intermediate motor median nerve conduction velocities (usually between 25 and 60 m/s). It presents with moderately severe, slowly progressive usual clinical features of Charcot-Marie-Tooth disease (muscle weakness and atrophy of the distal extremities, distal sensory loss, reduced or absent deep tendon reflexes, feet deformities, extensor digitorum brevis atrophy). Findings in nerve biopsies include age-dependent axonal degeneration, reduced number of large myelinated fibers, segmental remyelination, and no onion bulbs. [from SNOMEDCT_US]

Clinical features

From HPO
Hand muscle weakness
MedGen UID:
66798
Concept ID:
C0239831
Finding
Reduced strength of the musculature of the hand.
Upper limb muscle weakness
MedGen UID:
305607
Concept ID:
C1698196
Finding
Weakness of the muscles of the arms.
Abnormal foot morphology
MedGen UID:
1762829
Concept ID:
C5399834
Anatomical Abnormality
An abnormality of the skeleton of foot.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
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.
Decreased sensory nerve conduction velocity
MedGen UID:
336512
Concept ID:
C1849148
Finding
Reduced speed of conduction of the action potential along a sensory nerve.
Axonal regeneration
MedGen UID:
340241
Concept ID:
C1854454
Finding
The presence of axonal regeneration following a previous axonal lesion.
Decreased motor nerve conduction velocity
MedGen UID:
388130
Concept ID:
C1858729
Finding
A type of decreased nerve conduction velocity that affects the motor neuron.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Difficulty running
MedGen UID:
108251
Concept ID:
C0560346
Finding
Reduced ability to run.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Charcot-Marie-Tooth disease dominant intermediate C in Orphanet.

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

Curated

Aretz S, Rautenstrauss B, Timmerman V
Eur J Hum Genet 2010 Sep;18(9) Epub 2010 May 26 doi: 10.1038/ejhg.2010.75. PMID: 20512157Free PMC Article

Recent clinical studies

Etiology

Pan Y, Kafaie J, Thomas FP
Muscle Nerve 2020 Jan;61(1):111-115. Epub 2019 Oct 17 doi: 10.1002/mus.26724. PMID: 31587308

Diagnosis

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

Prognosis

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

Clinical prediction guides

Pan Y, Kafaie J, Thomas FP
Muscle Nerve 2020 Jan;61(1):111-115. Epub 2019 Oct 17 doi: 10.1002/mus.26724. PMID: 31587308

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • EuroGenetest, 2010
      Clinical utility gene card for: HMSN/HNPP HMSN types 1, 2, 3, 6 (CMT1,2,4, DSN, CHN, GAN, CCFDN, HNA); HNPP

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