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Charcot-Marie-Tooth disease type 1E(CMT1E)

MedGen UID:
501212
Concept ID:
C3495591
Disease or Syndrome
Synonyms: Charcot-Marie-Tooth disease and deafness; Charcot-Marie-Tooth disease, demyelinating, Type 1E; Charcot-Marie-Tooth neuropathy and deafness, autosomal dominant; Charcot-Marie-Tooth Neuropathy Type 1E; CMT 1E
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): PMP22 (17p12)
 
Monarch Initiative: MONDO:0007311
OMIM®: 118300
Orphanet: ORPHA90658

Definition

A rare subtype of CMT1 characterized by a variable clinical presentation. Onset within the first two years of life with a delay in walking is not uncommon; however, onset may occur later. CMT1E is caused by point mutations in the <i>PMP22</i> (17p12) gene. The disease severity depends on the particular <i>PMP22</i> mutation, with some cases being very mild and even resembling hereditary neuropathy with liability to pressure palsies, while others having an earlier onset with a more severe phenotype (reminiscent of Dejerine-Sottas syndrome) than that seen in CMT1A, caused by gene duplication. These severe cases may also report deafness and much slower motor nerve conduction velocities compared to CMT1A patients. [from ORDO]

Clinical features

From HPO
Talipes calcaneovalgus
MedGen UID:
56270
Concept ID:
C0152237
Anatomical Abnormality
Talipes calcaneovalgus is a flexible foot deformity (as opposed to a rigid congenital vertical talus foot deformity) that can either present as a positional or structural foot deformity depending on severity and/or causality. The axis of calcaneovalgus deformity is in the tibiotalar joint, where the foot is positioned in extreme hyperextension. On inspection, the foot has an "up and out" appearance, with the dorsal forefoot practically touching the anterior aspect of the ankle and lower leg.
Limb muscle weakness
MedGen UID:
107956
Concept ID:
C0587246
Finding
Reduced strength and weakness of the muscles of the arms and legs.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
The presence of an unusually high plantar arch. Also called high instep, pes cavus refers to a distinctly hollow form of the sole of the foot when it is bearing weight.
Hammertoe
MedGen UID:
209712
Concept ID:
C1136179
Anatomical Abnormality
Hyperextension of the metatarsal-phalangeal joint with hyperflexion of the proximal interphalangeal (PIP) joint.
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.
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 middel fingers as far as oligo- or monodactyl hands.
Sensorineural hearing impairment
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
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.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction 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.
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.
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  

Recent clinical studies

Diagnosis

Jung NY, Kwon HM, Nam DE, Tamanna N, Lee AJ, Kim SB, Choi BO, Chung KW
Genes (Basel) 2022 Jul 8;13(7) doi: 10.3390/genes13071219. PMID: 35886002Free PMC Article

Clinical prediction guides

Jung NY, Kwon HM, Nam DE, Tamanna N, Lee AJ, Kim SB, Choi BO, Chung KW
Genes (Basel) 2022 Jul 8;13(7) doi: 10.3390/genes13071219. PMID: 35886002Free PMC Article

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