Brain Advance Access published online on June 23, 2003
Brain, doi:10.1093/brain/awg202
© 2003 by Guarantors of Brain
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Article
1 Department of Neurology, University Hospital La Fe, Valencia, Spain
* Corresponding author. E-mail: teresevillaus{at}yahoo.com.
Received 22 January 2003
; revised 29 March 2003
; accepted 16 April 2003
Three Spanish families with an autosomal recessive severe hereditary motor and sensory neuropathy, showing mutations in the ganglioside-induced-differentiation-associated protein 1 (GDAP1) gene in the Charcot-Marie-Tooth (CMT) type 4A locus were studied. The disorder started in the neonatal period or early infancy with weakness and wasting of the feet and, subsequently, involvement of the hands, causing severe disability. By the late teens, some patients developed a hoarse voice and vocal cord paresis. Peripheral motor nerve conduction velocity (MNCV) could not be measured in many cases because of the absence of muscle response due to distal atrophy. However, latencies to proximal muscles were in the normal range; median MNCV was >40 m/s in those cases in which it could be measured. Sural nerve biopsy from two patients showed a pronounced depletion of myelinated fibres, regenerative clusters and signs of axonal atrophy. Additionally, a small proportion of thin myelinated fibres and proliferation of Schwann cells forming onion bulb structures were also found. Unmyelinated fibre population was markedly increased. These findings are indicative of a predominant axonal degeneration with some demyelinating features. These Spanish families share in the severe CMT clinical phenotype with some Tunisian families who also presented mutations in the GDAP1 gene and to which the CMT4A locus was originally assigned. However, our families differ in the presence of laryngeal involvement and values of MNCV and pathological features are more in line with CMT2 type. The possibility that GDAP1 gene mutations could be expressed under different phenotypes is a question to be resolved.
Keywords: Charcot-Marie-Tooth disease type 2; hereditary motor and sensory neuropathy type II; vocal cord paresis, autosomal recessive; GDAP1 gene
Clinical, electrophysiological and morphological findings of Charcot-Marie-Tooth neuropathy with vocal cord palsy and mutations in the GDAP1 gene
2 Laboratory of Genetics and Molecular Medicine, Instituto de Biomedicina, Consejo Superior de Investigaciones Científicas (CSIC), Valencia, Spain
3 Department of Clinical Neurophysiology, University Hospital La Fe, Valencia, Spain
4 Department of Experimental Cellular Pathology, University Hospital La Fe, Valencia, Spain
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