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Charcot-Marie-Tooth disease axonal type 2F(CMT2F)

MedGen UID:
335784
Concept ID:
C1847823
Disease or Syndrome
Synonyms: Charcot-Marie-Tooth disease type 2F; Charcot-Marie-Tooth disease, neuronal, Type 2F; Charcot-Marie-Tooth Neuropathy Type 2F; CMT 2F; CMT2F
SNOMED CT: Autosomal dominant Charcot-Marie-Tooth disease type 2F (719510006)
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): HSPB1 (7q11.23)
 
Monarch Initiative: MONDO:0011687
OMIM®: 606595
Orphanet: ORPHA99940

Definition

A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy with symmetric weakness primarily occurring in the lower limbs and reaching the arms only after 5 to 10 years, occasional and predominantly distal sensory loss and reduced tendon reflexes. Presents with gait anomaly between the first and sixth decade and early onset is generally associated to a more severe phenotype that may include foot drop. [from SNOMEDCT_US]

Clinical features

From HPO
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
Hyporeflexia of upper limbs
MedGen UID:
323007
Concept ID:
C1836835
Finding
Reduced intensity of muscle tendon reflexes in the upper limbs. Reflexes are elicited by stretching the tendon of a muscle, e.g., by tapping.
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.
Ulnar claw
MedGen UID:
871311
Concept ID:
C4025799
Congenital Abnormality
An abnormal hand position characterized by hyperextension of the fourth and fifth fingers at the metacarpophalangeal joints and flexion of the interphalangeal joints of the same fingers such that they are curled towards the palm.
Fasciculations
MedGen UID:
5124
Concept ID:
C0015644
Sign or Symptom
Fasciculations are observed as small, local, involuntary muscle contractions (twitching) visible under the skin. Fasciculations result from increased irritability of an axon (which in turn is often a manifestation of disease of a motor neuron). This leads to sporadic discharges of all the muscle fibers controlled by the axon in isolation from other motor units.
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.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Decreased motor nerve conduction velocity
MedGen UID:
388130
Concept ID:
C1858729
Finding
A type of decreased nerve conduction velocity that affects the motor neuron.
Chronic axonal neuropathy
MedGen UID:
867220
Concept ID:
C4021578
Disease or Syndrome
An abnormality characterized by chronic impairment of the normal functioning of the axons.
Muscle spasm
MedGen UID:
52431
Concept ID:
C0037763
Sign or Symptom
Sudden and involuntary contractions of one or more muscles.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Distal lower limb amyotrophy
MedGen UID:
324515
Concept ID:
C1836451
Disease or Syndrome
Muscular atrophy of distal leg muscles.
Upper limb amyotrophy
MedGen UID:
867165
Concept ID:
C4021523
Disease or Syndrome
Muscular atrophy involving the muscles of the upper limbs.
Claw hand deformity
MedGen UID:
1814631
Concept ID:
C5702555
Anatomical Abnormality
An abnormality of the hand characterized by metacarpophalangeal (MCP) hyperextension and proximal interphalangeal (PIP) and distal interphalangeal (DIP) flexion. The position of the affected hand is said to resemble a claw.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Charcot-Marie-Tooth disease axonal type 2F in Orphanet.

Recent clinical studies

Etiology

Greenbaum L, Ben-David M, Nikitin V, Gera O, Barel O, Hersalis-Eldar A, Shamash J, Shimshoviz N, Reznik-Wolf H, Shohat M, Dominissini D, Pras E, Dori A
Ann Clin Transl Neurol 2021 Jun;8(6):1260-1268. Epub 2021 May 11 doi: 10.1002/acn3.51362. PMID: 33973728Free PMC Article
Schwartz NU
Neurobiol Dis 2019 Oct;130:104505. Epub 2019 Jun 15 doi: 10.1016/j.nbd.2019.104505. PMID: 31212070

Diagnosis

Shen X, Zhang J, Zhan F, Tian W, Jiang Q, Luan X, Zhang X, Cao L
Biomolecules 2022 Sep 27;12(10) doi: 10.3390/biom12101382. PMID: 36291591Free PMC Article
Greenbaum L, Ben-David M, Nikitin V, Gera O, Barel O, Hersalis-Eldar A, Shamash J, Shimshoviz N, Reznik-Wolf H, Shohat M, Dominissini D, Pras E, Dori A
Ann Clin Transl Neurol 2021 Jun;8(6):1260-1268. Epub 2021 May 11 doi: 10.1002/acn3.51362. PMID: 33973728Free PMC Article
Katz M, Davis M, Garton FC, Henderson R, Bharti V, Wray N, McCombe P
J Neurol Sci 2020 Jun 15;413:116809. Epub 2020 Mar 27 doi: 10.1016/j.jns.2020.116809. PMID: 32334137
Tanabe H, Higuchi Y, Yuan JH, Hashiguchi A, Yoshimura A, Ishihara S, Nozuma S, Okamoto Y, Matsuura E, Ishiura H, Mitsui J, Takashima R, Kokubun N, Maeda K, Asano Y, Sunami Y, Kono Y, Ishigaki Y, Yanamoto S, Fukae J, Kida H, Morita M, Tsuji S, Takashima H
J Peripher Nerv Syst 2018 Mar;23(1):40-48. Epub 2018 Feb 14 doi: 10.1111/jns.12252. PMID: 29381233Free PMC Article

Therapy

Shen S, Benoy V, Bergman JA, Kalin JH, Frojuello M, Vistoli G, Haeck W, Van Den Bosch L, Kozikowski AP
ACS Chem Neurosci 2016 Feb 17;7(2):240-58. Epub 2015 Dec 7 doi: 10.1021/acschemneuro.5b00286. PMID: 26599234Free PMC Article
Srivastava AK, Renusch SR, Naiman NE, Gu S, Sneh A, Arnold WD, Sahenk Z, Kolb SJ
Neurobiol Dis 2012 Aug;47(2):163-73. Epub 2012 Apr 11 doi: 10.1016/j.nbd.2012.03.035. PMID: 22521462Free PMC Article

Prognosis

Greenbaum L, Ben-David M, Nikitin V, Gera O, Barel O, Hersalis-Eldar A, Shamash J, Shimshoviz N, Reznik-Wolf H, Shohat M, Dominissini D, Pras E, Dori A
Ann Clin Transl Neurol 2021 Jun;8(6):1260-1268. Epub 2021 May 11 doi: 10.1002/acn3.51362. PMID: 33973728Free PMC Article
Schwartz NU
Neurobiol Dis 2019 Oct;130:104505. Epub 2019 Jun 15 doi: 10.1016/j.nbd.2019.104505. PMID: 31212070

Clinical prediction guides

Holmgren A, Bouhy D, De Winter V, Asselbergh B, Timmermans JP, Irobi J, Timmerman V
Acta Neuropathol 2013 Jul;126(1):93-108. Epub 2013 Jun 1 doi: 10.1007/s00401-013-1133-6. PMID: 23728742Free PMC Article
Srivastava AK, Renusch SR, Naiman NE, Gu S, Sneh A, Arnold WD, Sahenk Z, Kolb SJ
Neurobiol Dis 2012 Aug;47(2):163-73. Epub 2012 Apr 11 doi: 10.1016/j.nbd.2012.03.035. PMID: 22521462Free PMC Article

Recent systematic reviews

Taga A, Cornblath DR
J Peripher Nerv Syst 2020 Sep;25(3):223-229. Epub 2020 Jul 8 doi: 10.1111/jns.12395. PMID: 32639100

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