Investigators from Wayne State University found that five genetic subtypes of Charcot-Marie-Tooth disease accounted for more than 99 percent of diagnoses
Editor's note: This story was updated Feb. 4, 2011, to reflect the availability of a paper and editorial on this subject in Annals of Neurology.
Results of genetic testing done at Wayne State University in Detroit of more than 1,000 people suspected of having Charcot-Marie-Tooth (CMT) disease were presented by MDA grantee Michael Shy and colleagues April 14, 2010, at the annual meeting of the American Academy of Neurology, held in Toronto.
The new results suggest that the Wayne State CMT population is representative of the CMT population as a whole. A flow chart to guide physicians who test for CMT can be developed based on these results, the investigators proposed.
Charcot-Marie-Tooth disease is a disorder of the peripheral nerves, fibers that run between the spinal cord and the periphery of the body, transmitting sensory and motor (movement-related) information.
More than 30 forms of CMT have been identified, related to various gene defects in the nerve fibers themselves or in a sheath made of myelin that surrounds and insulates each nerve fiber.
Genetic diagnosis for CMT can be challenging and expensive, so there's a need for better testing guidelines.
About the new findings
MDA grantee Michael Shy, a professor at the Center for Molecular Medicine and Genetics at Wayne State University in Detroit, and colleagues, examined testing results from 1,019 patients suspected of having CMT who were seen at Wayne State.
They said 782 (77 percent) ultimately received confirmation of a CMT diagnosis.
A specific genetic diagnosis was made for 519 of the 782 (66 percent), while no mutation was identified in 263 of the patients (34 percent).
The most common CMT subtypes were CMT1A (PMP22 gene duplications or point mutations, chromosome 17); CMT1X (connexin 32 gene, X chromosome); HNPP (PMP22 gene deletions or point mutations, chromosome 17); CMT1B (myelin protein 0 gene, chromosome 1); and CMT2A (mitofusin 2 gene, chromosome 1).
Fewer than 1 percent of the patients in whom a genetic diagnosis was made had other subtypes of CMT.
Meaning for people with CMT
If a flow chart that can guide doctors to faster, more cost-effective CMT testing can be developed, more people with CMT may benefit from such testing. As treatments that are specific to certain genetic subtypes of CMT are developed, the results of such tests are likely to become important in medical management of the disease.
In the meantime, results of genetic testing can help people understand the inheritance pattern and the likely level of severity of the disease in their families.
Editor's note 2/4/11: A paper with flow charts to guide physicians in ordering genetic testing for CMT is now available in Annals of Neurology at Charcot-Marie-Tooth disease subtypes and genetic testing strategies, with an accompanying editorial available at The death panel for Charcot-Marie-Tooth panels.