ABSTRACT
Charcot-Marie-Tooth (CMT) disease is a hereditary neuropathy of motor and sensory impairment with distal predominance. Atrophy and weakness of lower limbs are the first signs of the disease. It can be classified, with the aid of electromyography and nerve conduction studies, as demyelinating (CMT1) or axonal (CMT2). OBJECTIVE: Clinical and neurophysiological investigation of a large multigenerational family with CMT2 with autosomal dominant mode of transmission. METHOD: Fifty individuals were evaluated and neurophysiological studies performed in 22 patients. RESULTS: Thirty individuals had clinical signs of motor-sensory neuropathy. Babinski sign was present in 14 individuals. Neurophysiological study showed motor-sensory axonal polyneuropathy. CONCLUSION: The clinical and neurophysiological characteristics of this family does not differ from those observed with other forms of CMT, except for the high prevalence of Babinski sign.
A doença de Charcot-Marie-Tooth (CMT) é uma neuropatia hereditária de acometimento sensitivo e motor de predomínio distal. Atrofia e fraqueza em membros inferiores são os primeiros sinais da doença. Pode ser classificada, com auxílio da eletroneuromiografia, em desmielinizante (CMT1) ou axonal (CMT2). OBJETIVO: Investigação clínica e neurofisiológica de família com portadores de CMT2 de herança dominante. MÉTODO: Foi feita avaliação neurológica de 50 indivíduos e eletroneuromiografia em 22 pacientes. RESULTADOS: Trinta indivíduos tinham sinais clínicos de neuropatia sensitivo-motora. Sinal de Babinski estava presente em 14 indivíduos. A eletroneuromiografia demonstrou polineuropatia axonal sensitiva e motora. CONCLUSÃO: As características clínicas e neurofisiológicas desta família não se diferem das observadas em outras formas de CMT, exceto pela alta prevalência de sinal de Babinski.
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Charcot-Marie-Tooth Disease/physiopathology , Pyramidal Tracts/physiopathology , Charcot-Marie-Tooth Disease/genetics , Electromyography/methods , Genetic Linkage/genetics , Pedigree , PhenotypeABSTRACT
Frecuency of the allele causing the axonal form of autosomal recessive Charcot-Marie-Tooth in Palmares, Costa Rica. The Charcot-Marie-Tooth disease constitutes is among the most frequent hereditary peripheral neuropathies world-wide. We identified a family from Palmares (Alajuela, Costa Rica) with 18 affected members. Their neuropathy is axonal, with an autosomal recessive pattern of inheritance; the responsible gene is at the 19q13.33 chromosomal region. Later the mutation was identified in gene MED25. We studied the frequency and geographic distribution of the mutant allele. In a random sample of 103 individuals, six were heterozygote and were widely distributed in Palmares. There was no person in homozigote state for the mutant allele. Clinical characteristics do not differ significantly between individuals that are homozygous for the wildtype allele and individuals hetero zygous for the mutation. A 5.83 % of the population is heterozygote and the frequency of the Ala335Val allele is 0.029, six times higher than in a sample of the Costa Rican population. Werecommend a molecular analysis of carriers to detect additional cases in the region. Rev. Biol. Trop. 57 (Suppl.1): 381-387. Epub 2009 November 30.
La enfermedad de Charcot-Marie-Tooth constituye elgrupo de neuropatías periféricas hereditarias más común a nivel mundial. Una familia con 18 afectados del cantón de Palmares (Alajuela, Costa Rica) con una neuropatía de tipo axonal y herencia autosómica recesiva, permitió localizar el gen responsable en la región 19q13.33. Posteriormente se identificó la mutación causante en el gen MED25. El presente estudio determinó la frecuencia del alelo mutante, así como la distribución geográfica de este alelo. En una muestra al azar de 103 individuos se encontraron seis individuos heteroigotas para la mutación, distribuidos por todo el cantón. No se encontró ninguna persona en estado homocigota para este alelo. No hallamos algunacaracterística clínica que difiera significativamente entre los individuos homocigotos silvestres y los heterocigotos para la mutación. El 5.83% de la población es heterocigota y la frecuencia del alelo Ala335Val es de 0.029, seis veces mayor que en una muestra de toda la población costarricense. Por esta razón se recomienda un análisis molecular de portadores con el fin de alertar sobre la posibilidad de aparición de más casos en el cantón.
Subject(s)
Humans , Molecular Structure , Charcot-Marie-Tooth Disease/diagnosis , Gene Frequency , Costa RicaABSTRACT
BACKGROUND: Mutations in the myelin protein zero (MPZ) gene, which is located on chromosome 1q21-q22, is present in Charcot-Marie-Tooth disease type 1B (CMT1B), CMT type 2, Dejerine-Sottas syndrome, and congenital hypomyelination neuropathy. It is proposed that the nature and position of the MPZ mutations mainly determine the axonal and demyelinating phenotypes. In this study, we investigated to determine the clinical and electrophysiological characteristics in CMT patients with mutations in the MPZ gene. METHODS: We examined mutations of MPZ, in 62 Korean families diagnosed as having CMT disease. Mutations were confirmed by through both strands sequencing. Nerve conduction studies were carried out in CMT patients having each mutation. RESULTS: The three mutations (Asp118Asn, c.449-1G>T (3'-splice site), Lys236Glu), determined to be novel, were not detected in the 105 healthy controls. The mutation frequency of MPZ was similar as those found in several European populations. Electrophysiologically, 3'-splice site mutation (449-1G>T) showed the conduction block and moderate slowing nerve conduction velocities like that of CMT1B. However, the other mutations represented the electrophysiological features of CMT type 2. CONCLUSIONS: We report the identified three novel MPZ mutations in Korean CMT patients and the phenotype-genotype correlations based on nerve conduction studies.