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Charcot-Marie-Tooth disease type 2E(CMT2E)

MedGen UID:
375127
Concept ID:
C1843225
Disease or Syndrome
Synonyms: Charcot-Marie-Tooth disease, axonal, Type 2E; Charcot-Marie-Tooth Neuropathy Type 2E/1F; CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2E; CMT 2E; CMT2E
SNOMED CT: Autosomal dominant Charcot-Marie-Tooth disease type 2E (717012004)
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): NEFL (8p21.2)
 
Monarch Initiative: MONDO:0011894
OMIM®: 607684
Orphanet: ORPHA99939

Definition

A form of axonal Charcot-Marie-Tooth disease a peripheral sensorimotor neuropathy. Onset is in the first to sixth decade with a gait anomaly and a leg weakness that reaches the arms secondarily. Tendon reflexes are reduced or absent and after years all patients have a pes cavus. Other signs may be present including hearing loss and postural tremor. [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).
Hammertoe
MedGen UID:
209712
Concept ID:
C1136179
Anatomical Abnormality
Hyperextension of the metatarsal-phalangeal joint with hyperflexion of the proximal interphalangeal (PIP) joint.
Lower limb muscle weakness
MedGen UID:
324478
Concept ID:
C1836296
Finding
Weakness of the muscles of the legs.
Distal lower limb muscle weakness
MedGen UID:
324514
Concept ID:
C1836450
Finding
Reduced strength of the distal musculature of the legs.
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.
Distal upper limb muscle weakness
MedGen UID:
461970
Concept ID:
C3150620
Finding
Reduced strength of the distal musculature of the arms.
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.
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.
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.
Impaired pain sensation
MedGen UID:
373348
Concept ID:
C1837522
Finding
Reduced ability to perceive painful stimuli.
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.
Impaired distal vibration sensation
MedGen UID:
381262
Concept ID:
C1853767
Finding
A decrease in the ability to perceive vibration in the distal portions of the limbs.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Decreased motor nerve conduction velocity
MedGen UID:
388130
Concept ID:
C1858729
Finding
A type of decreased nerve conduction velocity that affects the motor neuron.
Decreased distal sensory nerve action potential
MedGen UID:
870474
Concept ID:
C4024920
Finding
A reduction in the amplitude of sensory nerve action potential in distal nerve segments. This feature is measured by nerve conduction studies.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Hand muscle atrophy
MedGen UID:
116091
Concept ID:
C0239830
Finding
Muscular atrophy involving the muscles of the hand.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Facial palsy
MedGen UID:
87660
Concept ID:
C0376175
Disease or Syndrome
Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Frequent falls
MedGen UID:
163408
Concept ID:
C0850703
Finding
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Increased connective tissue
MedGen UID:
400898
Concept ID:
C1866021
Finding
The presence of an abnormally increased amount of connective tissue.
Nemaline bodies
MedGen UID:
814369
Concept ID:
C3808039
Finding
Nemaline rods are abnormal bodies that can occur in skeletal muscle fibers. The rods can be observed on histological analysis of muscle biopsy tissue or upon electron microscopy, where they appear either as extensions of sarcomeric Z-lines, in random array without obvious attachment to Z-lines (often in areas devoid of sarcomeres) or in large clusters localized at the sarcolemma or intermyofibrillar spaces.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

Term Hierarchy

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

Recent clinical studies

Clinical prediction guides

Stone EJ, Uchida A, Brown A
Cytoskeleton (Hoboken) 2019 Jul;76(7-8):423-439. Epub 2019 Nov 6 doi: 10.1002/cm.21566. PMID: 31574566Free PMC Article
Villalón E, Dale JM, Jones M, Shen H, Garcia ML
Brain Res 2015 Nov 19;1627:143-53. Epub 2015 Sep 28 doi: 10.1016/j.brainres.2015.09.024. PMID: 26423936Free PMC Article
Adebola AA, Di Castri T, He CZ, Salvatierra LA, Zhao J, Brown K, Lin CS, Worman HJ, Liem RK
Hum Mol Genet 2015 Apr 15;24(8):2163-74. Epub 2014 Dec 30 doi: 10.1093/hmg/ddu736. PMID: 25552649Free PMC Article
Shen H, Barry DM, Dale JM, Garcia VB, Calcutt NA, Garcia ML
Hum Mol Genet 2011 Jul 1;20(13):2535-48. Epub 2011 Apr 14 doi: 10.1093/hmg/ddr152. PMID: 21493625Free PMC Article
De Jonghe P, Mersivanova I, Nelis E, Del Favero J, Martin JJ, Van Broeckhoven C, Evgrafov O, Timmerman V
Ann Neurol 2001 Feb;49(2):245-9. doi: 10.1002/1531-8249(20010201)49:2<245::aid-ana45>3.0.co;2-a. PMID: 11220745

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