CMT 2A: Predictability of MFN2 Testing in a Large CMT Clinic

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Predictability of MFN2 Testing in a Large CMT Clinic

(ANN April 17, 2008)

a M. E. Feely, Carly E. Siskind, Francies, E. Shy,

Detroit, MI

OBJECTIVE: To determine the prevalence of severe or mild axonal

neuropathies in patients with Charcot Marie Tooth disease type 2A

(CMT2A).

BACKGROUND: CMT2A comprises 20% of patients with CMT2 and is caused

by mutations in the Mitofusin 2 (MFN2) gene. CMT2A patients may have

severe axonal neuropathies beginning in infancy or late onset

neuropathies with moderate to mild phenotypes. The distribution of

these phenotypes is poorly characterized. Knowing the likelihood of

patients having a mutation in the MFN2 can help direct genetic

testing.

DESIGN/METHODS: The frequency of positive test results for MFN2

mutations was compared for patients with severe, early onset axonal

neuropathy and mild to moderate, late onset neuropathy in 75 patients

seen at the Wayne State University CMT clinic. Severity was assessed

by the CMT Neuropathy Score (CMTNS). The age of onset, family

history, and disease progression was recorded.

RESULTS: Sixteen of the 75 tested patients were classified as severe

(CMTNS>21) and 59 were mild (CMTNS<10) or moderate (CMTNS 11-20).

Fourteen of 16 severe patients (8 of 10 families), but none of the

59 mild to moderate patients (56 families), had MFN2 mutations. Seven

of the 8 distinct mutations were de novo and 3 mutations not

previously reported. All patients with a mutation had a childhood

onset and no severe patient older than 20 was ambulatory. Optic

atrophy was seen in 5 of the 14 patients. The patients testing

negative for MFN2 mutations had an average age of onset of 35 years,

mild to moderate neuropathy scores, and all remained ambulatory. One

of these individuals had optic atrophy.

CONCLUSIONS/RELEVANCE: MFN2 mutations are more likely to be

identified in patients with severe, childhood onset axonal

neuropathies and are very likely to be de novo mutations. Milder,

late onset axonal neuropathies were unlikely to be CMT2A in our

clinic population.