What is Charcot-Marie-Tooth (CMT) disease type 1A?

Updated: Feb 19, 2019
  • Author: Francisco de Assis Aquino Gondim, MD, PhD, MSc, FAAN; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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Approximately 85% of patients develop clinical evidence of disease before age 20 years. In one large series, 34 patients were classified as having a classic CMT phenotype, whereas 27 patients had additional features such as CNS features, diabetes mellitus, and prominent muscle cramps. [15] Forty-five of 61 patients had deficits in their hands. Loss of large- and small-fiber sensory function, ranging from mostly mild to moderately severe, was reported in 43 patients. Tremor occurred in up to 25% of patients. Whether it was incidental or part of the syndrome is controversial. Tremor with CMT is referred to as Roussy-Levy syndrome.

One Austrian family with CMT1A had slow progression and predominantly proximal arm weakness and wasting. [16] Sleep apnea was described in a French family with CMT1A (a feature previously reported in Charcot-Marie-Tooth disease type 2C [CMT2C]); most family members were asymptomatic, but sleep apnea correlated with the severity of the neuropathy, possibly because of pharyngeal neuropathy. Two sisters had an atypical CMT1A phenotype consisting of prominent sensory symptoms, tremor, and episodes of acute paralysis. [17]

Recent studies of DSS or hereditary motor and sensory neuropathy type 3 demonstrated that point mutations in PMP22 are a common cause, as are homozygous PMP22 deletions.

Clinical progression is slow in the second to fourth decades of life; therefore, any change in pace must lead to a consideration of superimposed acquired or possibly independently inherited forms of neuromuscular diseases. The authors have reported the association of McArdle disease and CMT1A in 2 patients who had subacute dramatic worsening of their CMT.

The severity of the CMT1A phenotype can also possibly increase over time, being more severe in new generations for unknown reasons.

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