MFN2 Gene Mutations in Young Children with Clinically Sporadic Axonal Sensorimot

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MFN2 Gene Mutations in Young Children with Clinically Sporadic Axonal

Sensorimotor Polyneuropathy

(AAN April 17, 2008)

Archana Narasimha, Yum, Harold Marks, Philadelphia, PA

OBJECTIVE: To determine the frequency of mitofusin 2 (MFN2) gene

mutations in young children with clinically sporadic axonal

sensorimotor polyneuropathy (CSASP).

BACKGROUND: MFN2 gene mutations are found in approximately 20% of

patients with familial CMT-2. Many patients have an early onset and

severe disease course. The association of MFN2 mutations in CSASP is

not known.

DESIGN/METHODS: We retrospectively analyzed the medical records of

all children under 10 years of age with CSASP who were screened for

MFN2 mutations. Data was abstracted from all patients who were

diagnosed after April 2005.

RESULTS: We identified 5 children who met the above criteria. Four of

them had MFN2 mutations. One child had a previously reported disease

associated mutation. All of them had missense mutations. Two children

had the same mutation which is in the highly conserved GTPase domain

of the MFN2 gene. In children harboring the MFN2 mutations, average

age of onset was 2.25 years (range 1-3 years). Average time for

progression to the upper extremities was 3.6 years. In 3, CSF protein

was normal. EMG-NCS demonstrated an axonal sensorimotor neuropathy in

all of them. Nerve biopsy in 2 revealed an axonal neuropathy. None of

them had a family history of Charcot Marie Tooth disease and the 7

parents examined (3 were not available) had a normal neurological

examination. One parent had a normal EMG-NCS.

CONCLUSIONS/RELEVANCE: Although limited, this study suggests that

mutations of the MFN2 gene are the most common cause of CSASP in

young children (<5 yrs) and that the evaluation of young children

with CSASP should begin with a screen of the MFN2 gene. Our data also

supports the observation that children with MFN2 mutations may have

early onset of symptoms and a severe disease course.