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Charcot-Marie-Tooth Disease Clinical Presentation

  • Author: Divakara Kedlaya, MBBS; Chief Editor: Vinod K Panchbhavi, MD, FACS  more...
Updated: Mar 14, 2016


Patients with Charcot-Marie-Tooth (CMT) disease have a significant family history. This history varies depending on the inheritance and penetrance pattern of the particular disorder (see Causes). Spontaneous mutations also have been reported.

The age of presentation varies, depending on the type of CMT disease. Onset usually occurs in the first two decades of life.

Slowly progressing weakness beginning in the distal limb muscles generally is noted; it typically occurs in the lower extremities before it affects the upper ones. A subgroup of patients with CMT 1A may present with proximal muscle wasting and weakness.

Patients initially may complain of difficulty walking and frequent tripping due to foot and distal leg weakness. Frequent ankle sprains and falls are characteristic. Parents may report that a child is clumsy or simply not very athletic. As weakness becomes more severe, foot drop commonly occurs. Steppage (that is, gait in which the individual must lift the leg in an exaggerated fashion to clear the foot off of the ground) also is common.

Intrinsic foot muscle weakness commonly results in the foot deformity known as pes cavus. Symptoms related to structural foot abnormalities include calluses, ulcers, cellulitis, and lymphangitis.

Hand weakness results in complaints of poor finger control, poor handwriting, difficulty using zippers and buttons, and clumsiness in manipulating small objects. The hand may be affected at all ages in children with CMT 1A; that hand problems in these patients may be underrecognized in the early stages of disease, causing potential delay in therapy.[34]

Patients usually do not complain of numbness. This may be because patients with CMT disease never had normal sensation and, therefore, simply do not perceive their lack of sensation.

Pain (musculoskeletal and neuropathic types) may be present. Muscle cramping is a common complaint.[35]

Autonomic symptoms usually are absent, but a few men with CMT disease have reported impotence.


Physical Examination

Distal muscle wasting may be noted in the legs, resulting in the characteristic stork leg or inverted champagne bottle appearance.

Bony abnormalities commonly seen in long-standing CMT disease include pes cavus (high-arch foot), probably analogous to the development of claw hand in ulnar nerve lesion. Pes cavus has an occurrence rate of 25% in the first decade of life and 67% in later decades. Selective denervation of intrinsic foot musculature (particularly of the lumbricals), rather than imbalance of lower-leg muscles, seems to be the initial mechanism causing reduced ankle flexibility and forefoot cavus deformity.[36] Other foot deformities also can occur (see the image below).

Foot deformities in a 16-year-old boy with Charcot Foot deformities in a 16-year-old boy with Charcot-Marie-Tooth disease type 1A.

Spinal deformities (eg, thoracic scoliosis) occur in 37-50% of patients with CMT 1.

Deep tendon reflexes (DTRs) are markedly diminished or are absent. Vibration sensation and proprioception are significantly decreased, but patients usually have no sensory symptoms.

Patients may have sensory gait ataxia, and a Romberg test usually yields positive results. The Romberg test is performed by having the patient stand upright with the feet together and the eyes closed. The examiner observes the patient's body movement relative to a perpendicular object behind him or her (eg, a door or window). Pronounced, sometimes irregular swaying, or occasionally even toppling over, constitutes a positive result. The key point is that the patient's unsteadiness increases when his or her eyes are closed.

Sensation of pain and temperature is usually intact. Essential tremor is present in 30-50% of patients with CMT disease. Sensory neuronal hearing loss is observed in 5% of patients. Enlarged and palpable peripheral nerves are common. Phrenic nerve involvement with diaphragmatic weakness is rare but has been described. Vocal cord involvement and hearing loss can occur in rare forms of CMT disease.



Because of the loss of protective sensation distally in all four limbs, patients with CMT disease are susceptible to skin breakdown or burns, nonhealing foot ulcers, and, in severe cases, bony deformities of bilateral feet. As mentioned previously, orthoses are required for treatment of foot drop or to accommodate bony foot deformities. If not fitted properly, the orthoses themselves become a source of skin breakdown secondary to associated distal sensory impairment.

The presence of maternal CMT disease is associated with an increased risk of complications during delivery. This increase is related to a higher frequency of emergency interventions during birth.[32]

Contributor Information and Disclosures

Divakara Kedlaya, MBBS Clinical Associate Professor, Department of Physical Medicine and Rehabilitation, Loma Linda University School of Medicine; Medical Director, Physical Medicine and Rehabilitation and Pain Management, St Mary Corwin Medical Center

Divakara Kedlaya, MBBS is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, Colorado Medical Society, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Vinod K Panchbhavi, MD, FACS Professor of Orthopedic Surgery, Chief, Division of Foot and Ankle Surgery, Director, Foot and Ankle Fellowship Program, Department of Orthopedics, University of Texas Medical Branch School of Medicine

Vinod K Panchbhavi, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, American Orthopaedic Association, American Orthopaedic Foot and Ankle Society, Orthopaedic Trauma Association, Texas Orthopaedic Association

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Styker.

Additional Contributors

James K DeOrio, MD Associate Professor of Orthopedic Surgery, Duke University School of Medicine

James K DeOrio, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Foot and Ankle Society

Disclosure: Received royalty from Merete for other; Received royalty from SBi for other; Received royalty from BioPro for other; Received honoraria from Acumed, LLC for speaking and teaching; Received honoraria from Wright Medical Technology, Inc for speaking and teaching; Received honoraria from SBI for speaking and teaching; Received honoraria from Integra for speaking and teaching; Received honoraria from Datatrace Publishing for speaking and teaching; Received honoraria from Exactech, Inc for speaking a.

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Foot deformities in a 16-year-old boy with Charcot-Marie-Tooth disease type 1A.
Charcot-Marie-Tooth disease type 1A DNA test showing duplication in the short arm of chromosome 17 (A); compared with normal (B).
Nerve conduction study showing decreased nerve conduction velocity in the median nerve in an 18-year-old woman with Charcot-Marie-Tooth disease type 1.
Table 1. Charcot-Marie-Tooth Disorders: Genetic and Clinical Feature Comparison
CMT Type Chromosome; Inheritance Pattern Age of Onset Clinical Features Average NCVs§
CMT 1A (PMP-22 dupl.) 17p11; AD* First decade Distal weakness 15-20 m/s
CMT 1B (P0 -MPZ)** 1q22; AD First decade Distal weakness <20 m/s
CMT 1C (non A, non B) 16p13;AD Second decade Distal weakness 26-42 m/s
CMT 1D (early growth response [EGR]–2)#[[22] 24] 10q21; AD First decade Distal weakness 15-20 m/s
CMT 1E 17p11; AD First decade Distal weakness, deafness 15-20 m/s
CMT 1F 8p21; AD First decade Distal weakness 15-20 m/s
CMT X (Connexin-32)[23, 24, 25, 26, 27] Xq13; XD Second decade Distal weakness 25-40 m/s
CMT 2A 1p36; AD 10 y Distal weakness >38 m/s
CMT 2B 3q; AD Second decade Distal weakness,

sensory loss, skin ulcers

Axon loss; Normal
CMT 2C 12q23-q24, AD First decade Vocal cord, diaphragm, and

distal weakness

>50 m/s
CMT 2D 7p14; AD 16-30 y Distal weakness, upper limb predominantly Axon loss; N††
CMT 2E 8p21; AD 10-30 y Distal weakness, lower limb predominantly Axon loss; N
CMT 2F 7q11-q21; AD 15-25 y Distal weakness Axon loss; N
CMT 2G 12q12-q13; ?AD 9-76 y Distal weakness Axon loss; N
CMT 2H ?; AR 15-25 y Distal weakness, Pyramidal features Axon loss; N
CMT 2I 1q22; AD 47-60 y Distal weakness Axon loss; N
CMT 2J 1q22; AD 40-50 y Distal weakness, hearing loss Axon loss; N
CMT 2K 8q13-q21; AR <4 y Distal weakness Axon loss; N
CMT 2L 12q24; AD 15-25 y Distal weakness Axon loss; N
CMT R-Ax (Ouvrier) AR First decade Distal weakness Axon loss; N
CMT R-Ax (Moroccan) 1q21; AR Second decade Distal weakness Axon loss; N
Cowchock syndrome Xq24-q26 First decade Distal weakness, deafness, mental retardation Axon loss; N
HNPP|| (PMP-22)

Or tomaculous neuropathy

17p11; AD All ages Episodic weakness and numbness Conduction Blocks
Dejerine-Sottas syndrome (DSS) or hereditary motor and sensory neuropathy (HMSN) 3 P0; AR

PMP-22; AD

8q23; AD

2 y Severe weakness <10 m/s

hypomyelination (CH)

P0, EGR2 or PMP-22


Birth Severe weakness < 10 m/s
CMT 4A 8q13; AR Childhood Distal weakness Slow

(Myotubular in-related


11q23; AR 2-4 y Distal and proximal


CMT 4C 5q23; AR 5-15 y Delayed walking 14-32 m/s
CMT 4D (Lom)

(N-myc Downstream-

Regulated Gene 1)

8q24; AR 1-10 y Distal muscle wasting, foot and hand deformities 10-20 m/s
CMT 4E (EGR2) 10q21; AR Birth Infant hypotonia 9-20 m/s
CMT 4G 10q23.2; AR 8-16 years Distal weakness 9-20 m/s
CMT 4H 12p11.21-q13.11; AR 0-2 years Delayed walking 9-20 m/s
CMT 4F 19q13; AR 1-3 y Motor delay Absent
*Autosomal dominant

†Autosomal recessive

‡X-linked dominant

§Nerve conduction velocities

||Hereditary neuropathy with liability to pressure palsy

¶Peripheral myelin protein

#Early growth response

**Myelin protein zero


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