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Charcot-Marie-Tooth Disease Differential Diagnoses

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

Diagnostic Considerations

In addition to the conditions listed in the differential diagnosis, other problems to be considered include the following:

  • Acquired nongenetic causes of peripheral neuropathies
  • Vitamin B12 deficiency
  • Vasculitis
  • Amyloid associated with chronic inflammation
  • Occult malignancy
  • Heavy-metal intoxication
  • Chronic inflammatory demyelinating polyneuropathy
  • Motor neuropathy with multiple conduction block
  • Other genetic neuropathies
  • Familial brachial plexus neuropathy (ie, hereditary neuralgic amyotrophy)
  • Autosomal recessive genetic disorders, such as Refsum disease or metachromatic leukodystrophy
  • X-linked recessive genetic disorders, such as adrenomyeloneuropathy or Pelizaeus-Merzbacher disease
  • Amyloid neuropathies
  • Hereditary ataxias with neuropathy (eg, Friedreich ataxia)

Blindness, seizures, dementia, and mental retardation are not part of Charcot-Marie-Tooth syndrome.

Differential Diagnoses

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 TypeChromosome; Inheritance PatternAge of OnsetClinical FeaturesAverage NCVs§
CMT 1A (PMP-22 dupl.)17p11; AD*First decadeDistal weakness15-20 m/s
CMT 1B (P0 -MPZ)**1q22; ADFirst decadeDistal weakness<20 m/s
CMT 1C (non A, non B)16p13;ADSecond decadeDistal weakness26-42 m/s
CMT 1D (early growth response [EGR]–2)#[[22] 24] 10q21; ADFirst decadeDistal weakness15-20 m/s
CMT 1E17p11; ADFirst decadeDistal weakness, deafness15-20 m/s
CMT 1F8p21; ADFirst decadeDistal weakness15-20 m/s
CMT X (Connexin-32)[23, 24, 25, 26, 27] Xq13; XDSecond decadeDistal weakness25-40 m/s
CMT 2A1p36; AD10 yDistal weakness>38 m/s
CMT 2B3q; ADSecond decadeDistal weakness,

sensory loss, skin ulcers

Axon loss; Normal
CMT 2C12q23-q24, ADFirst decadeVocal cord, diaphragm, and

distal weakness

>50 m/s
CMT 2D7p14; AD16-30 yDistal weakness, upper limb predominantlyAxon loss; N††
CMT 2E8p21; AD10-30 yDistal weakness, lower limb predominantlyAxon loss; N
CMT 2F7q11-q21; AD15-25 yDistal weaknessAxon loss; N
CMT 2G12q12-q13; ?AD9-76 yDistal weaknessAxon loss; N
CMT 2H?; AR15-25 yDistal weakness, Pyramidal featuresAxon loss; N
CMT 2I1q22; AD47-60 yDistal weaknessAxon loss; N
CMT 2J1q22; AD40-50 yDistal weakness, hearing lossAxon loss; N
CMT 2K8q13-q21; AR<4 yDistal weaknessAxon loss; N
CMT 2L12q24; AD15-25 yDistal weaknessAxon loss; N
CMT R-Ax (Ouvrier)ARFirst decadeDistal weaknessAxon loss; N
CMT R-Ax (Moroccan)1q21; ARSecond decadeDistal weaknessAxon loss; N
Cowchock syndromeXq24-q26First decadeDistal weakness, deafness, mental retardationAxon loss; N
HNPP|| (PMP-22)

Or tomaculous neuropathy

17p11; ADAll agesEpisodic weakness and numbnessConduction Blocks
Dejerine-Sottas syndrome (DSS) or hereditary motor and sensory neuropathy (HMSN) 3P0; AR

PMP-22; AD

8q23; AD

2 ySevere weakness<10 m/s

hypomyelination (CH)

P0, EGR2 or PMP-22


BirthSevere weakness< 10 m/s
CMT 4A8q13; ARChildhoodDistal weaknessSlow

(Myotubular in-related


11q23; AR2-4 yDistal and proximal


CMT 4C5q23; AR5-15 yDelayed walking14-32 m/s
CMT 4D (Lom)

(N-myc Downstream-

Regulated Gene 1)

8q24; AR1-10 yDistal muscle wasting, foot and hand deformities10-20 m/s
CMT 4E (EGR2)10q21; ARBirthInfant hypotonia9-20 m/s
CMT 4G10q23.2; AR8-16 yearsDistal weakness9-20 m/s
CMT 4H12p11.21-q13.11; AR0-2 yearsDelayed walking9-20 m/s
CMT 4F19q13; AR1-3 yMotor delayAbsent
*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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