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Charcot-Marie-Tooth disease axonal type 2K(CMT2K)

MedGen UID:
375064
Concept ID:
C1842983
Disease or Syndrome
Synonyms: Charcot-Marie-Tooth disease type 2K; Charcot-Marie-Tooth disease, axonal, autosomal recessive, Type 2K; CHARCOT-MARIE-TOOTH NEUROPATHY, AXONAL, TYPE 2K
SNOMED CT: Autosomal recessive Charcot-Marie-Tooth disease with hoarseness (725047007); Autosomal recessive axonal Charcot-Marie-Tooth disease type 2K (725047007)
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).
 
Genes (locations): GDAP1 (8q21.11); JPH1 (8q21.11)
 
Monarch Initiative: MONDO:0011916
OMIM®: 607831
Orphanet: ORPHA101097

Definition

A severe early-onset form of axonal Charcot-Marie-Tooth peripheral sensorimotor polyneuropathy. Onset occurs in the neonatal period or early infancy with a clinical picture including hypotonia, scoliosis, a hoarse voice, vocal cord paralysis and respiratory insufficiency. However, nerve conduction velocities and pathological findings from sural nerve biopsies are indicative of a predominantly axonal neuropathy with some demyelinating features. Caused by mutations in the GDAP1 gene (8q13.3), encoding a protein required for mitochondrial fission. [from SNOMEDCT_US]

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).
Split hand
MedGen UID:
397570
Concept ID:
C2699510
Congenital Abnormality
A condition in which middle parts of the hand (fingers and metacarpals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic middle fingers over absent middle fingers as far as oligo- or monodactyl hands.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Axonal regeneration
MedGen UID:
340241
Concept ID:
C1854454
Finding
The presence of axonal regeneration following a previous axonal lesion.
Decreased number of peripheral myelinated nerve fibers
MedGen UID:
346872
Concept ID:
C1858285
Finding
A loss of myelinated nerve fibers in the peripheral nervous system (in general, this finding can be observed on nerve biopsy).
Decreased motor nerve conduction velocity
MedGen UID:
388130
Concept ID:
C1858729
Finding
A type of decreased nerve conduction velocity that affects the motor neuron.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Kyphoscoliosis
MedGen UID:
154361
Concept ID:
C0575158
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
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 axonal type 2K in Orphanet.

Recent clinical studies

Etiology

Figueiredo FB, Silva WA Jr, Giuliatti S, Tomaselli PJ, Lourenço CM, Gouvêa SP, Covaleski APPM, Hallak JE, Marques W Jr
Neuromuscul Disord 2021 Jun;31(6):505-511. Epub 2021 Mar 20 doi: 10.1016/j.nmd.2021.03.005. PMID: 33903021
Kanwal S, Perveen S
J Pak Med Assoc 2019 Feb;69(2):241-243. PMID: 30804591

Diagnosis

Padilha JPD, Brasil CS, Hoefel AML, Winckler PB, Donis KC, Brusius-Facchin AC, Saute JAM
Clin Genet 2020 Aug;98(2):185-190. Epub 2020 Jun 29 doi: 10.1111/cge.13793. PMID: 32506583
Cassereau J, Chevrollier A, Codron P, Goizet C, Gueguen N, Verny C, Reynier P, Bonneau D, Lenaers G, Procaccio V
Exp Neurol 2020 Jan;323:113069. Epub 2019 Oct 23 doi: 10.1016/j.expneurol.2019.113069. PMID: 31655048
Kanwal S, Perveen S
J Pak Med Assoc 2019 Feb;69(2):241-243. PMID: 30804591

Prognosis

Kabzińska D, Kotruchow K, Cegielska J, Hausmanowa-Petrusewicz I, Kochański A
Acta Biochim Pol 2014;61(4):739-44. Epub 2014 Oct 22 PMID: 25337607

Clinical prediction guides

Figueiredo FB, Silva WA Jr, Giuliatti S, Tomaselli PJ, Lourenço CM, Gouvêa SP, Covaleski APPM, Hallak JE, Marques W Jr
Neuromuscul Disord 2021 Jun;31(6):505-511. Epub 2021 Mar 20 doi: 10.1016/j.nmd.2021.03.005. PMID: 33903021
Fu J, Dai S, Lu Y, Wu R, Wang Z, Yuan Y, Lv H
Neuromuscul Disord 2017 Aug;27(8):760-765. Epub 2017 Apr 20 doi: 10.1016/j.nmd.2017.04.001. PMID: 28495047
Pla-Martín D, Calpena E, Lupo V, Márquez C, Rivas E, Sivera R, Sevilla T, Palau F, Espinós C
Hum Mol Genet 2015 Jan 1;24(1):213-29. Epub 2014 Aug 28 doi: 10.1093/hmg/ddu440. PMID: 25168384

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