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Clinical, electrophysiological and morphological findings of Charcot-Marie-Tooth neuropathy with vocal cord palsy and mutations in the GDAP1 gene.
Brain. 2003 Sep; 126(Pt 9):2023-33.B

Abstract

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.

Authors+Show Affiliations

Servicio de Neurología, Hospital Universitari La Fe, Avenida Campanar 21, 46009 Valencia, Spain. teresevillaus@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12821518

Citation

Sevilla, Teresa, et al. "Clinical, Electrophysiological and Morphological Findings of Charcot-Marie-Tooth Neuropathy With Vocal Cord Palsy and Mutations in the GDAP1 Gene." Brain : a Journal of Neurology, vol. 126, no. Pt 9, 2003, pp. 2023-33.
Sevilla T, Cuesta A, Chumillas MJ, et al. Clinical, electrophysiological and morphological findings of Charcot-Marie-Tooth neuropathy with vocal cord palsy and mutations in the GDAP1 gene. Brain. 2003;126(Pt 9):2023-33.
Sevilla, T., Cuesta, A., Chumillas, M. J., Mayordomo, F., Pedrola, L., Palau, F., & Vílchez, J. J. (2003). Clinical, electrophysiological and morphological findings of Charcot-Marie-Tooth neuropathy with vocal cord palsy and mutations in the GDAP1 gene. Brain : a Journal of Neurology, 126(Pt 9), 2023-33.
Sevilla T, et al. Clinical, Electrophysiological and Morphological Findings of Charcot-Marie-Tooth Neuropathy With Vocal Cord Palsy and Mutations in the GDAP1 Gene. Brain. 2003;126(Pt 9):2023-33. PubMed PMID: 12821518.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical, electrophysiological and morphological findings of Charcot-Marie-Tooth neuropathy with vocal cord palsy and mutations in the GDAP1 gene. AU - Sevilla,Teresa, AU - Cuesta,Ana, AU - Chumillas,María José, AU - Mayordomo,Fernando, AU - Pedrola,Laia, AU - Palau,Francesc, AU - Vílchez,Juan J, Y1 - 2003/06/23/ PY - 2003/6/25/pubmed PY - 2003/10/25/medline PY - 2003/6/25/entrez SP - 2023 EP - 33 JF - Brain : a journal of neurology JO - Brain VL - 126 IS - Pt 9 N2 - 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. SN - 0006-8950 UR - https://www.unboundmedicine.com/medline/citation/12821518/Clinical_electrophysiological_and_morphological_findings_of_Charcot_Marie_Tooth_neuropathy_with_vocal_cord_palsy_and_mutations_in_the_GDAP1_gene_ L2 - https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/awg202 DB - PRIME DP - Unbound Medicine ER -