What is the role of lab tests in the workup of Charcot-Marie-Tooth disease (CMT)?

Updated: Jun 23, 2021
  • Author: Divakara Kedlaya, MBBS; Chief Editor: Elizabeth A Moberg-Wolff, MD  more...
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Answer

Results of all routine laboratory tests are within the reference range in Charcot-Marie-Tooth disease (CMT). Specific genetic tests are available for some types of CMT. A study by Murphy et al demonstrates that a molecular diagnosis can currently be achieved in over 60% of patients with CMT. [63] A molecular diagnosis is much more likely in patients with CMT-1 rather than CMT-2. Four genes commonly available for testing, PMP22 ( CMT-1A-PMP22 gene duplication; HNPP-PMP22 gene deletion), GJB1 ( CMT-1X), MPZ ( CMT-1B ), and MFN2 ( CMT-2A) account for over 90% of all CMT molecular diagnoses.

It is possible to narrow down the most likely gene based on nerve conduction studies and family history. Flow charts have been published using nerve conduction velocities to direct genetic testing, usually with the aid of family history information. [64]

  • CMT-1A - Pulsed-field gel electrophoresis or a specialized fluorescent in situ hybridization (FISH) assay is the most reliable genetic test to detect PMP22 gene duplication in CMT-1A and PMP22 gene deletion in HNPP. [65] DNA-based testing for the PMP22 duplication (CMT-1A) is widely available and detects more than 98% of patients with CMT-1A (see following image). Point mutations in the PMP-22 gene cause fewer than 2% of cases of CMT-1A and are identified by this technique. Approximately 70-80% of cases of CMT-1 are designated as CMT-1A, caused by duplication of the PMP-22 gene (locus 17p11). [16, 66] See the image below.

    Charcot-Marie-Tooth disease type 1A DNA test showi Charcot-Marie-Tooth disease type 1A DNA test showing duplication in the short arm of chromosome 17 (A) compared with normal (B).
  • CMT-1B - Genetic testing is performed primarily on a research basis, but it is available from a few commercial laboratories. Approximately 5-10% of CMT-1 is designated CMT-1B and is caused by a point mutation in the myelin P0 protein (MPZ) gene (chromosomal locus 1q22). [20, 67]

  • CMT-1C and CMT-1D - Very rarely, mutations occur in the EGR-2 (early growth response 2) gene or in the LITAF gene, causing CMT-1D and CMT-1C, respectively, for which molecular genetic testing also is clinically available.

  • CMT-2 - Clinically indistinguishable, the 4 subtypes of CMT-2 are distinguished solely from genetic linkage findings. The relative proportions of CMT-2A, CMT-2B, CMT-2C, and CMT-2D have not yet been determined. The chromosomal loci for CMT-2A, CMT-2B, CMT-2C, CMT-2D, CMT-2E, CMT-2F, CMT-2G, and CMT-2L have been mapped, but the genes have not been identified. Molecular genetic testing is clinically available only for CMT-2A, CMT-2B1, CMT-2E, and CMT-2F.

  • CMT-X - Molecular genetic testing of the GJB1 (Cx32) gene detects about 90% of cases. Such testing is clinically available.


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