CMT 1A: Duplication with severe paresis of proximal lower limb muscles: a long t

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J Neurol Neurosurg Psychiatry. 2006 Jun 20

Charcot-Marie-Tooth disease type 1A duplication with severe paresis

of proximal lower limb muscles: a long-term follow-up study.

Berciano J, Gallardo E, A, Infante J, Mateo I, Combarros O.

University Hospital " Marques de Valdecilla, Spain.

OBJECTIVE: To describe a large CMT-1A duplication pedigree where

severe pelvic and thigh musculature weakness occurred in two cases

analyzing the MRI leg muscle atrophy pattern.

METHODS: The pedigree comprises 18 examined patients, aged between 15

and 85 years (median, 46), serially evaluated for up to three

decades. All 18 patients and 13 non-affected at-risk individuals had

electrophysiological examination. MRI study of lower limb musculature

was performed in four patients. Three patients had sural nerve

biopsy. Genetic testing was performed in 17 patients and all 13 at-

risk normal subjects.

RESULTS: Fourteen patients were asymptomatic or slightly disabled.

The two oldest patients, aged 85 and 80, showed a moderate phenotype.

The remaining two patients, aged 70 and 53, showed late onset and

gradually progressive peroneal paresis extending up to thigh and

pelvic musculature rending gait waddling.

In all three scanned patients with mild phenotype MRI showed subtle

and subclinical fatty infiltration of calf antero-lateral muscle

compartments with thigh muscle involvement in one, and extensive

atrophy of intrinsic foot muscles. In the youngest patient with

proximal leg weakness, MRI showed massive fatty atrophy of all calf

muscles, postero-medial thigh muscle compartments, and internal and

external hip rotator muscles.

Sural nerve biopsies showed hypertrophic neuropathy with no

superimposed inflammation. There was good correlation between

electrophysiological and genetic testing.

CONCLUSIONS: Late in the clinical course a small proportion of CMT-1A

patients develop severe proximal leg weakness, long-term follow-up

being essential for its detection. MRI may show subclinical

involvement of thigh musculature.