Charcot-marie-tooth disease subtypes and genetic testing strategies.

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Ann Neurol. 2011 Jan;69(1):22-33

Charcot-marie-tooth disease subtypes and genetic testing strategies.

Saporta AS, Sottile SL, LJ, Feely SM, Siskind CE, Shy ME.

Department of Neurology, Wayne State University, Detroit, MI.

Abstract

OBJECTIVE: Charcot-Marie-Tooth disease (CMT) affects 1 in 2,500 people and is

caused by mutations in more than 30 genes. Identifying the genetic cause of CMT

is often necessary for family planning, natural history studies, and for entry

into clinical trials. However genetic testing can be both expensive and

confusing to patients and physicians.

METHODS: We analyzed data from 1,024 of our patients to determine the percentage

and features of each CMT subtype within this clinic population. We identified

distinguishing clinical and physiological features of the subtypes that could be

used to direct genetic testing for patients with CMT.

RESULTS: Of 1,024 patients evaluated, 787 received CMT diagnoses. A total of 527

patients with CMT (67%) received a genetic subtype, while 260 did not have a

mutation identified. The most common CMT subtypes were CMT1A, CMT1X, hereditary

neuropathy with liability to pressure palsies (HNPP), CMT1B, and CMT2A. All

other subtypes accounted for less than 1% each. Eleven patients had >1

genetically identified subtype of CMT. Patients with genetically identified CMT

were separable into specific groups based on age of onset and the degree of

slowing of motor nerve conduction velocities.

INTERPRETATION: Combining features of the phenotypic and physiology groups

allowed us to identify patients who were highly likely to have specific subtypes

of CMT. Based on these results, we propose a strategy of focused genetic testing

for CMT, illustrated in a series of flow diagrams created as testing guides.