A Case of Demyelinating CMT Neuropathy with MFN2 Gene Mutations

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A Case of Demyelinating Charcot Marie Tooth Neuropathy with MFN2 Gene

Mutations

(AAN April 17, 2008)

Arnaud Lacour, Helene Zephir, Olivier Outteryck, Jean-François

Hurtevent, Lille, France, Metropolitan, Philippe Latour, Lyon,

France, Vallat, Limoges, Cedex, France, Vermersch,

Lille, France

OBJECTIVE: To describe a new Charcot Marie Tooth (CMT) phenotype

related with MFN2 gene mutations.

BACKGROUND: MFN2 gene mutations are a major cause of CMT2.

Demyelinating CMT has never been reported with MFN2 mutations.

RESULTS: A 48 year-old woman was investigated for progressive walking

difficulties since the age of 25 year-old, without familial history.

Neurological exam showed bilateral pes cavus, areflexia of the lower

limbs, an asymmetrical (left-sided) distal weakness of the four limbs

and a decreased vibration sense. Electromyography (EMG) revealed

heterogeneous demyelination with slow conduction velocities (< 30

m/s) and temporal dispersions of motor action potentials. CMT1A and

CMTX were ruled out by normal PMP22 and GJB1 gene screenings. A major

loss of large myelinated fibers with onion bulbs was noticed on sural

nerve biopsy. MFN2 direct sequencing revealed two mutations: R468H

(described in both CMT2 and healthy subjects) and a new G387A

mutation; Her father, who showed no signs of neuropathy and a normal

EMG, was heterozygous carrier of the R468H mutation while the mother

was found to be heterozygous for the G387A mutation. Although her EMG

was normal, neurological examination noticed weak tendon reflexes in

the lower limbs and a muscle atrophy of the left leg.

CONCLUSIONS/RELEVANCE: This is the first description of a clear

demyelinating CMT neuropathy related to MFN2 mutations. We

hypothesized that the particular combination of these two mutations

could lead to a new phenotype.