Charcot-Marie-Tooth disease

Case history #1

A 45-year-old man presents with a bilateral steppage gait (lifting legs up excessively to clear the toes), foot numbness, and difficulty with buttons. His birth history was normal, and early motor milestones were achieved on time. He began walking at 13 months, and was noted to be a "toe-walker." As a child he ran toward the middle to the back of his peers and was never able to ice skate because of weak ankles. He first noted problems with walking in his early twenties, tripping often and falling once a month, and has started having problems with his hands in the last 5 years. Nerve conduction studies show symmetrical nerve slowing to 23 m/second (normal >50 m/second) with mildly reduced amplitudes and prolonged distal latencies. Sensory responses are absent. His father was noted to have the same symptoms, and genetic testing reveals a duplication of the PMP22 gene, providing a diagnosis of CMT1A.

Case history #2

A 30-year-old woman presents with severe leg weakness and distal arm weakness. Her birth history was normal and early motor milestones were achieved on time. She began to have trouble with foot-drop and falling in her preschool and school-age years. The foot-drop and weakness in the proximal muscles progressed through her teens, so that walking up stairs became very difficult. She required a wheelchair for primary ambulation at 20 years of age. On examination, her hands are atrophied and contractures are present causing an "en griffe" appearance, and weakness extends proximally. The sensory examination is mostly normal. Nerve conduction studies show no motor or sensory responses. However, she has brought studies from childhood showing normal conduction velocities and severely reduced amplitudes, indicative of axonal degeneration. She has no family history of weakness or neuropathy. Genetic testing reveals a mutation in the MFN2 gene, providing a diagnosis of CMT2A.

Other presentations

The most common features of Charcot-Marie-Tooth (CMT) disease are weakness and atrophy of the lower leg and foot. High-arched feet and hammertoes (pes cavus) are common but not pathognomonic. Most patients present with difficulties walking, twisting of the ankles, and slapping of the feet. Features are normally symmetric, although asymmetries may occasionally occur. The majority of patients remain ambulatory, although they may need braces and other assistive devices. Severe cases also exist.

Children with delayed motor milestones, who never ran or ambulated, have a severe early-onset phenotype of CMT1, CMT2, and CMT4 called Dejerine-Sottas syndrome.

Hereditary neuropathy with liability to pressure palsies (HNPP) presents with transient sensory and motor symptoms after minor compression or stretching of a nerve. These symptoms can last weeks to months and are usually asymmetric.

Some forms of CMT are solely motor or sensory and are known as hereditary motor neuropathy and hereditary sensory neuropathy, respectively.