Charcot-Marie-Tooth disease comprises a group of hereditary peripheral neuropathies with different genetic abnormalities.
Absence of a family history does not rule out the condition.
Key features include clumsiness as a child, weak ankles, symmetrical nerve conduction changes, and a steppage gait (lifting legs up excessively to clear the toes).
Pes cavus (high foot arches with hammertoes) and distal atrophy of the hands and legs are characteristic.
Genetic testing should be carefully considered.
Appropriate rehabilitative and orthotic treatments can keep patients highly functional.
Charcot-Marie-Tooth (CMT) disease, also known as hereditary motor and sensory neuropathy (HMSN), encompasses the majority of hereditary peripheral neuropathies. Both motor and sensory nerves are typically affected, with symmetrical changes noted on nerve conduction studies. Nerve conductions can be either demyelinating (velocity <38 m/second in ulnar nerve), or axonal (reduced amplitudes with >38 m/second velocity), or have features of both. CMT is a genetically heterogeneous condition, with over 90 genes and loci known to cause the condition when mutated.
History and exam
Key diagnostic factors
- family history of neuropathy, pes cavus, or abnormal gait
- walking difficulties
- pes cavus
- steppage gait
- diffuse deep tendon hyporeflexia or areflexia
- reduced muscle strength
- reduced sensation
- transient sensory symptoms
- transient motor symptoms
Other diagnostic factors
- past surgery to feet and ankles
- balance difficulties in childhood
- ankle weakness
- sensory abnormalities in hands and feet
- delayed motor milestones without ambulation
- sensory ataxia
- family history of neuropathy, pes cavus (high foot arches with hammertoes), or abnormal gait
1st investigations to order
- nerve conduction studies (NCS)
Investigations to consider
- genetic testing
Carly E. Siskind, MS, CGCL
Clinical Assistant Professor (Affiliated)
Certified Genetic Counselor
Stanford Health Care
CES has an unpaid position on the Charcot Marie Tooth Association Advisory Board and is part of the Charcot Marie Tooth Disease Gene Curation Expert Panel for ClinGen. CES has professional relationships with some authors of references cited in this topic.
Dr Carly E. Siskind would like to gratefully acknowledge Prof Richard A Lewis, her previous co-contributor to this topic. RAL is a consultant for Pharnext, CSL Behring, and Axelacare. He is on the Medical Advisory Board for GBS-CIDP Foundation, MGFA, and MGF of Ca. He has done expert testimony related to GBS, CIDP, and other neurologic disorders, and educational talks for AAN, AANEM, CSL Behring, and Optioncare. With the exception of Pharnext, none of these relationships are related to Charcot-Marie-Tooth disease. RAL is an author of a number of references cited in this topic.
Pavel Seeman, MD, PhD
Associate Professor (Doc)
Head of the DNA Laboratory
Department of Child Neurology
Second School of Medicine
and University Hospital Motol
PS declares that he has no competing interests.
Kinga Szigeti, MD, PhD
Department of Neurology and Molecular and Human Genetics
Baylor College of Medicine
KS is an author of a reference cited in this topic.
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