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Charcot-Marie-Tooth disease axonal type 2S(CMT2S)

MedGen UID:
863786
Concept ID:
C4015349
Disease or Syndrome
Synonyms: CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL RECESSIVE, TYPE 2S; CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2S
SNOMED CT: Charcot-Marie-Tooth disease type 2S (1187617004)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): IGHMBP2 (11q13.3)
 
Monarch Initiative: MONDO:0014511
OMIM®: 616155
Orphanet: ORPHA443073

Definition

Charcot-Marie-Tooth disease type 2S is a relatively pure form of autosomal recessive axonal neuropathy characterized by onset in the first decade of slowly progressive distal muscle weakness and atrophy affecting the lower and upper limbs. Patients have decreased reflexes and variable distal sensory impairment (summary by Cottenie et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210). [from OMIM]

Clinical features

From HPO
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Upper limb muscle weakness
MedGen UID:
305607
Concept ID:
C1698196
Finding
Weakness of the muscles of the arms.
Lower limb muscle weakness
MedGen UID:
324478
Concept ID:
C1836296
Finding
Weakness of the muscles of the legs.
Areflexia of lower limbs
MedGen UID:
347285
Concept ID:
C1856694
Finding
Inability to elicit tendon reflexes in the lower limbs.
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.
Areflexia of upper limbs
MedGen UID:
388832
Concept ID:
C2674177
Finding
Inability to elicit tendon reflexes in the upper limbs.
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.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Sensorimotor neuropathy
MedGen UID:
207266
Concept ID:
C1112256
Disease or Syndrome
Axonal degeneration
MedGen UID:
332464
Concept ID:
C1837496
Finding
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Tongue atrophy
MedGen UID:
66828
Concept ID:
C0241423
Finding
Wasting of the tongue.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCharcot-Marie-Tooth disease axonal type 2S

Recent clinical studies

Etiology

Holbrook SE, Hicks AN, Martin PB, Hines TJ, Castro HP, Cox GA
Hum Mol Genet 2024 Oct 7;33(20):1800-1814. doi: 10.1093/hmg/ddae116. PMID: 39128026Free PMC Article

Diagnosis

Kulshrestha R, Forrester N, Antoniadi T, Willis T, Sethuraman SK, Samuels M
Neuromuscul Disord 2018 Dec;28(12):1016-1021. Epub 2018 Oct 5 doi: 10.1016/j.nmd.2018.09.008. PMID: 30409445
Yuan JH, Hashiguchi A, Yoshimura A, Yaguchi H, Tsuzaki K, Ikeda A, Wada-Isoe K, Ando M, Nakamura T, Higuchi Y, Hiramatsu Y, Okamoto Y, Takashima H
J Hum Genet 2017 Jun;62(6):599-604. Epub 2017 Mar 9 doi: 10.1038/jhg.2017.15. PMID: 28202949

Clinical prediction guides

Holbrook SE, Hicks AN, Martin PB, Hines TJ, Castro HP, Cox GA
Hum Mol Genet 2024 Oct 7;33(20):1800-1814. doi: 10.1093/hmg/ddae116. PMID: 39128026Free PMC Article
Martin PB, Holbrook SE, Hicks AN, Hines TJ, Bogdanik LP, Burgess RW, Cox GA
Hum Mol Genet 2023 Apr 6;32(8):1276-1288. doi: 10.1093/hmg/ddac283. PMID: 36413117Free PMC Article