Physical Medicine and Rehabilitation for Charcot-Marie-Tooth Disease Differential Diagnoses

Diagnostic Considerations

These include the following:

• Acquired nongenetic causes of peripheral neuropathies
• Vitamin B-12 deficiency
• Diabetes mellitus
• 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

• Alcoholism
• Chronic Myelogenous Leukemia
• Leprosy Neuropathy
• Neurosyphilis
• Pediatric HIV Infection

Workup

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

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.

Michael T Andary, MD, MS Professor, Residency Program Director, Department of Physical Medicine and Rehabilitation, Michigan State University College of Osteopathic Medicine

Michael T Andary, MD, MS is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, Association of Academic Physiatrists

Disclosure: Received honoraria from Allergan for speaking and teaching.

Chief Editor

Robert H Meier, III, MD Director, Amputee Services of America; Active Medical Staff, Presbyterian/St Luke’s Hospital, Spalding Rehabilitation Hospital, Select Specialty Hospital; Consulting Staff, Kindred Hospital

Robert H Meier, III, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, Association of Academic Physiatrists

Milton J Klein, DO, MBA Consulting Physiatrist, Heritage Valley Health System-Sewickley Hospital and Ohio Valley General Hospital

Milton J Klein, DO, MBA is a member of the following medical societies: American Academy of Disability Evaluating Physicians, American Academy of Medical Acupuncture, American Academy of Osteopathy, American Academy of Physical Medicine and Rehabilitation, American Medical Association, American Osteopathic Association, American Osteopathic College of Physical Medicine and Rehabilitation, American Pain Society, Pennsylvania Medical Society

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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.

Foot of 29-year-old with advanced Charcot-Marie-Tooth disease type 1.

Hands of 29-year-old with advanced Charcot-Marie-Tooth disease type 1.

Right ulnar motor nerve conduction study in a 29-year-old patient with advanced Charcot-Marie-Tooth disease type 1.

Left ulnar motor nerve conduction study in 29-year-old patient with advanced Charcot-Marie-Tooth disease type 1.

• Table. Charcot-Marie-Tooth Disorders: Genetic and Clinical Feature Comparison

Table. 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.)	17p11.2; AD*	First decade	Distal weakness	15-20 m/s
CMT-1B (P0 -MPZ)**	1q23.3; AD	First decade	Distal weakness	< 20 m/s
CMT-1C (non-A, non-B) (LITAF)	16p13.13;AD	Second decade	Distal weakness	26-42 m/s
CMT-1D (EGR-2)	10q21.3; AD	First decade	Distal weakness	15-20 m/s
CMT-1E (PMP22)	17p11.2; AD	First decade	Distal weakness, deafness	15-20 m/s
CMT-1F (NEFL)	8p21.2; AD	First decade	Distal weakness	15-20 m/s
CMT-X (connexin-32)	Xq13; XD	Second decade	Distal weakness	25-40 m/s
CMT-2A	1p36; AD	10 y	Distal weakness	>38 m/s
CMT-2B	3q21; 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	8q21; AD	15-25 y	Distal weakness, pyramidal features	Axon loss; N
CMT-2I	1q23; AD	47-60 y	Distal weakness	Axon loss; N
CMT-2J	1q23; AD	40-50 y	Distal weakness, hearing loss	Axon loss; N
CMT-2K	8q13-q21; AD	< 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 deletion) or tomaculous neuropathy	17p11; AD	All ages	Episodic weakness and numbness	Conduction Blocks
Dejerine-Sottas-syndrome (DSS) or HMSN-3	P0; AR PMP-22; AD 8q23; AD	2 y	Severe weakness	< 10 m/s
Congenital hypomyelination (CH)	P0, EGR-2 or PMP-22 AR	Birth	Severe weakness	< 10 m/s
CMT-4A	8q13; AR	Childhood	Distal weakness	Slow
CMT-4B (myotubularin- related protein 2)	11q23; AR	2-4 y	Distal and proximal weakness	Slow
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 (EGR-2)	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 ††Normal