Analysis of a Chinese pedigree with autosomal dominant Charcot-Marie-Tooth disease type 2A2A / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of a pedigree affected with peroneal muscular atrophy.@*METHODS@#Neuroelectrophysiological examination and whole exome sequencing were carried out for the proband, a six-year-and-ten-month-old boy. Suspected variant was verified in his family members through Sanger sequencing. Bioinformatic analysis was carried to predict the conservation of amino acid sequence and impact of the variant on the protein structure and function.@*RESULTS@#Electrophysiological examination showed demyelination and axonal changes of motor and sensory nerve fibers. A heterozygous missense c.1066A>G (p. Thr356Ala) variant was found in exon 11 of the MFN2 gene in the proband and his mother, but not in his sister and father. Bioinformatic analysis using PolyPhen-2 and Mutation Taster software predicted the variant to be pathogenic, and that the sequence of variation site was highly conserved among various species. Based no the American College of Medical Genetics and Genomics standards and guidelines, the c.1066A>G (p. Thr356Ala) variant of MFN2 gene was predicted to be likely pathogenic (PS1+ PM2+ PP3+ PP4).@*CONCLUSION@#The heterozygous missense c.1066A>G (p.Thr356Ala) variant of the MFN2 gene probably underlay the disease in the proband, and the results have enabled genetic counseling and prenatal diagnosis for this family.

Identification of a novel c.1A>G variant of GDAP1 gene in a pedigree affected with autosomal recessive fibula atrophy / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a pedigree affected with Charcot-Marie-Tooth (CMT) disease through high-throughput sequencing.@*METHODS@#Potential variants of the genes associated with CMT were screened by next-generation sequencing (NGS) of the members of the pedigree.@*RESULTS@#NGS has revealed that the two affected sisters both harbored homozygous c.1A>G variant of the GDAP1 gene, which caused replacement of the first amino acid Methionine by Valine (p.Met1Val). Their parents were both carriers of the heterozygous c.1A>G variant. The variant was unreported previously and has an extremely low frequency in the population. Meanwhile, one of the sisters and the mother also carried heterozygous c.710A>T variant of the BAG3 gene.@*CONCLUSION@#The homozygous c.1A>G variant of the GDAP1 gene probably underlay the CMT in both children. Above result has enabled clinical diagnosis and genetic counseling for this pedigree.

Charcot Marie Tooth disease (CMT4A) due to GDAP1 mutation: report of a colombian family / Enfermedad de Charcot Marie Tooth (CMT4A) por mutacion en el gen GDAP1: reporte de una familia colombiana

Background: Mutations of GDAP1 gene cause autosomal dominant and autosomal recessive Charcot-Marie-Tooth disease and more than 40 different mutations have been reported. The recessive Q163X mutation has been described in patients of Spanish ancestry, and a founder mutation in South American patients, originating in Spain has been demonstrated. Objective: We describe physical and histological features, and the molecular impact of mutation Q163X in a Colombian family. Methods: We report two female patients, daughters of consanguineous parents, with onset of symptoms within the first two years of life, developing severe functional impairment, without evidence of dysmorphic features, hoarseness or diaphragmatic paralysis. Electrophysiology tests showed a sensory and motor neuropathy with axonal pattern. Sequencing of GDAP1 gene was requested and the study identified a homozygous point mutation (c.487 C>T) in exon 4, resulting in a premature stop codon (p.Q163X). This result confirms the diagnosis of Charcot-Marie-Tooth disease, type 4A. Results: The patients were referred to Physical Medicine and Rehabilitation service, in order to be evaluated for ambulation assistance. They have been followed by Pulmonology service, for pulmonary function assessment and diaphragmatic paralysis evaluation. Genetic counseling was offered. The study of the genealogy of the patient, phenotypic features, and electrophysiological findings must be included as valuable tools in the clinical approach of the patient with Charcot-Marie-Tooth disease, in order to define a causative mutation. In patients of South American origin, the presence of GDAP1 gene mutations should be considered, especially the Q163X mutation, as the cause of CMT4A disease.

Antecedentes: Las mutaciones del gen GDAP1 son causantes de la enfermedad de Charcot Marie Tooth tanto autosómica dominante como recesiva, y se han reportado más de 40 mutaciones distintas. La mutación recesiva Q163X ha sido descrita en pacientes de ascendencia española y se ha demostrado una mutación fundadora originaria de España en pacientes de origen suramericano. Describimos las características físicas e histológicas y el impacto molecular de la mutación Q163X en una familia colombiana. Objetivo: Se describe el impacto de la mutación Q163X en las características físicas, histológicas y moleculares en una familia colombiana. Métodos: Se describe dos pacientes de sexo femenino, hijas de padres consanguíneos, quienes presentaron inicio de síntomas en los dos primeros años de vida, mostrando deterioro funcional severo, sin evidencia de dismorfía, disfonía o parálisis diafragmática. Los estudios de electrofisiología mostraron una neuropatía sensitiva y motora con patrón axonal. Se solicitó la secuenciación del gen GDAP1, y el estudio identificó una mutación homocigota puntual (c. 487 C>T) en el exón 4, causando un codón de parada prematuro (p. Q163X). Este resultado confirma el diagnóstico de Enfermedad de Charcot Marie Tooth, tipo 4A (recesiva, tipo axonal). Resultados: Las pacientes fueron remitidas al servicio de Fisiatría para evaluación de métodos de asistencia para deambulación. Ellas reciben seguimiento por el servicio de Neumología, quienes vigilan la función pulmonar y el desarrollo de parálisis diafragmática. Se brindó asesoramiento genético. La genealogía del paciente, las características fenotípicas y los hallazgos en los estudios electrofisiológicos son herramientas valiosas en el enfoque clínico del paciente con CMT, de forma que se pueda plantear una posible mutación causal. Se debe considerar la presencia de mutaciones en el gen GDAP1 en pacientes de origen suramericano, en especial la mutación Q163X, como causa de CMT4A.

A Costa Rican family affected with Charcot-Marie-Tooth disease due to the myelin protein zero (MPZ) p.Thr124Met mutation shares the Belgian haplotype / Una familia costarricense afectada por la enfermedad de Charcot-Marie-Tooth, debido a la mutación p.thr124Met en la proteína mielina cero (MPZ) compartida con el haplotipo belga

The p.Thr124Met mutation in the myelin protein zero (MPZ) causes the Charcot-Marie-Tooth disease type 2J, a peripheral neuropathy with additional symptoms as pupillary alterations and deafness. It was observed in several families around the world originating e. g. from Germany, Belgium, Japan, Italy and North America. Here we report Central American patients originating from a family in Costa Rica carrying this mutation. Clinical, electrophysiological and molecular analysis of patients and controls were performed, including gene and linked markers´ sequencing. Carriers share almost the entire haplotype with two non related Belgian CMT patients. As a result of the haplotype analysis, based on ten markers (seven SNPs, two microsatellites and an intronic polyA stretch), the founder effect hypothesis for this allele migration is suggestive. Rev. Biol. Trop. 62 (4): 1285-1293. Epub 2014 December 01.

La mutación p.thr124Met en la proteína mielina cero (MPZ) causa la enfermedad de Charcot-Marie-Tooth tipo 2J, una neuropatía periférica con síntomas adicionales como alteraciones pupilares y sordera. Se ha observado en varias familias alrededor del mundo, originarias de Alemania, Bélgica, Japón, Italia y Norteamérica, entre otras. Aquí reportamos a pacientes centroamericanos provenientes de Costa Rica que acarrean esta mutación. Se realizaron análisis clínico, electrofisiológico y molecular de pacientes y controles, incluyendo secuenciación del gen y de marcadores ligados a éste. Estos pacientes comparten casi por completo el haplotipo con dos pacientes belgas no emparentados. Como resultado del análisis de los haplotipos, basado en diez marcadores (siete SNPs, dos microsatélites y un elemento poli-A intrónico), se sugiere que se ha dado un efecto fundador en la migración de este alelo.

Clinical and neurophysiological investigation of a large family with dominant Charcot-Marie-Tooth type 2 disease with pyramidal signs / Investigação clínica e neurofisiológica de família com doença de Charcot-Marie-Tooth tipo 2 com sinais piramidais

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.

Distribución espacial de la enfermedad Charcot-Marie-Tooth en Costa Rica, 1990-2003 / Spatial distribution of the Charcot-Marie-Tooth disease in Costa Rica, 1990-2003

Objetivo: Evaluar la distribución espacial como indicador de la incidencia de la enfermedad de Charcot-Marie-Tooth por los egresos hospitalarios reportados en Costa Rica entre el período 1990-2003. Métodos: Se aplicó un rastreo estadístico espacial de la incidencia de la enfermedad y se evaluó la significancia estadística de los conglomerados con excesos de casos. Resultados: El exceso de casos observados de la enfermedad en la zona de Naranjo fue estadísticamente significativo (56 versus 26.3 p menor 0.05). Otras regiones en donde se presenta exceso significativo de casos de CMT, son: Tibás (33 versus 13.5), Alajuela Centro (20 versus 6), Turrialba centro (16 versus 4.5), Golfito (18 versus 5.6) y Puntarenas centro (9 versus 1.5). Discusión: Se propone este rastreo estadístico espacial como herramienta en el proceso de toma de decisiones paa disminuir la incidencia de la enfermedad, así como atender adecuadamente a los afectados por CMT y sus familias, pues el métoido identificó regiones críticas o conglomerados (clusters) en donde es necesario dirigir los esfuerzos para la evaluación de la incidencia de la enfermedad.

Objective: To evaluate the spatial distribution of Charcot- Marie-Tooth disease as indicator of incidence in Costa Rica between 1990-2003.Methods: A spatial statistical scan was performed for the CMT incidence. We evaluated the statistical significance of high rate clusters. Results: The excess of observed cases of the disease in the area of Naranjo was statistically significant (56 vs. 26.3 p <0.05). Other regions showing significant excess of cases of CMT are: Tibás (33 vs. 13.5), Alajuela Centro (20 vs. 6), Turrialba Centro (16 vs. 4.5), Golfito (18 vs. 5.6) and Puntarenas Centro (9 vs. 1.5).Discussion: Spatial statistical scan is proposed as a tool in the decision making process in order to reduce the incidence of the disease and respond appropriately to those affected by CMT and their families. The method identifies clusters where it is necessary to focus efforts in evaluating the incidence of the disease.

Diseño de microsondas mediante hibridación virtual para el estudio de variantes en los sitios REP-CMT1A / Microarray design using virtual hybridization to study variations in REP-CMT1A sites

Antecedentes: El gen PMP22 se encuentra duplicado en pacientes con Charcot-Marie-Tooth 1A (CMT1A); se ha descrito que el origen de la duplicación es el intercambio desigual de las cromátidas durante la meiosis entre dos regiones de 24 kb denominadas sitios REPCMT1A, encontrándose un REP proximal y un REP distal, los cuales tienen una homología de 98%. Dentro de cada uno de estos sitios existen zonas denominadas puntos calientes de mutación (hot spot), donde se presenta el mayor número de variantes y mutaciones que pudieran dar origen al intercambio desigual. El objetivo de este trabajo fue diseñar un conjunto de microsondas para elaborar un microarreglo con el cual pueda detectarse la presencia de variantes y puntos de mutación en los sitios REP-proximal y REP-distal CMT1A. Material y métodos A partir de las secuencias informadas de los REP distal y proximal, se delimitaron los sitios hot spot dentro de las regiones proximal y distal. Estas secuencias se alinearon, se empalmaron y se detectaron 12 zonas de diferencia secuencial. Resultados y conclusiones. Se diseñaron y analizaron 24 microsondas mediante el programa Genosensor Probe Designer. Las sondas podrán ser sintetizadas y utilizadas en un microarreglo que permita encontrar variaciones, puntos de mutación, y facilitar el diagnóstico de pacientes con CMT1A.

BACKGROUND: Gene PMP22 is duplicated in patients with CMT1A. Duplication is due to an unequal chromatid interchange during meiosis that takes place between two 24 Kb regions named REP-CMT1A proximal and distal sites. Homology is approximately 98%. Within each one of the sites we find zones termed hot spots where a greater number of variants and mutations could give origin to an unequal interchange. The aim of this study was to design a set of probes to create a microarray that could detect the presence of variants and mutation points in distal and proximal REP sites among patients with CMT1A. MATERIAL AND METHODS: With reported sequences of distal and proximal REPs, we determined hot spot sites within proximal and distal regions. These sequences were aligned and matched, hence 12 zones were detected. RESULTS AND CONCLUSIONS: Twenty four probes were designed and analyzed using the Genosensor Probe Designer program. Probes could be synthesized and used in a microarray that is able to find variations and mutation points and facilitates diagnosis of patients with CMT1A.

Distal hereditary motor neuropathy in Korean patients with a small heat shock protein 27 mutation

Distal hereditary motor neuropathy (dHMN) is a heterogeneous disorder characterized by degeneration of motor nerves in the absence of sensory abnormalities. Recently, mutations in the small heat shock protein 27 (HSP27) gene were found to cause dHMN type II or Charcot-Marie-Tooth disease type 2F (CMT2F). The authors studied 151 Korean axonal CMT or dHMN families, and found a large Korean dHMN type II family with the Ser135Phe mutation in HSP27. This mutation was inherited in an autosomal dominant manner, and was well associated with familial members with the dHMN phenotype. This mutation site is located in the ?-crystallin domain and is highly conserved between different species. The frequency of this HSP27 mutation in Koreans was 0.6%. Magnetic resonance imaging analysis revealed that fatty infiltrations tended to progressively extend distal to proximal muscles in lower extremities. In addition, fatty infiltrations in thigh muscles progressed to affect posterior and anterior compartments but to lesser extents in medial compartment, which differs from CMT1A patients presenting with severe involvements of posterior and medial compartments but less involvement of anterior compartment. The authors describe the clinical and neuroimaging findings of the first Korean dHMN patients with the HSP27 Ser135Phe mutation. To our knowledge, this is the first report of the neuroimaging findings of dHMN type II.

Estrategias para el diagnóstico clinico y molecular de Charcot-Marie-Tooth 1A: estudio en pacientes mexicanos / Strategies for clinical and molecular diagnosis of Charcot-Marie-Tooth 1A among Mexican patients

Antecedentes: La neuropatía periférica de Charcot-Marie-Tooth (CMT) es la enfermedad hereditaria más común del sistema nervioso periférico humano. El subtipo más frecuente, CMT1A, es asociado a una duplicación de un fragmento de ~1.5 Mb en 17p11.2-p12, que incluye al gen PMP22. Objetivo: Describir diferentes estrategias para el diagnóstico clínico y molecular de CMT1A en pacientes del Instituto Nacional de Rehabilitación. Material y métodos: A 17 pacientes estudiados clínica y electrofisiológicamente que reunieron los criterios para CMT1, se les realizó el estudio molecular mediante electroforesis capilar para detectar la duplicación del gen PMP22. Resultados: Los estudios clínico, bioquímico y electrofisiológico ofrecieron los criterios para establecer el diagnóstico de CMT1. Con la electroforesis capilar se detectó la duplicación del gen PMP22 en siete pacientes que fueron diagnosticados clínica y electrofisiológicamente como CMT1, pudiendo llegar al diagnóstico de CMT1A. Todas las duplicaciones identificadas fueron corroboradas mediante hibridación in situ fluorescente. Conclusión: Los resultados nos permiten asegurar que la electroforesis capilar es un método fácil y confiable para detectar la duplicación del gen PMP22. Además, el aplicar diferentes estrategias tanto clínicas, electrofisiológicas y moleculares en este tipo de pacientes, nos permitieron establecer el diagnóstico correcto y ofrecer asesoramiento genético adecuado.

BACKGROUND: Charcot-Marie-Tooth (CMT) is the most common inherited disorder of the human peripheral nerve. The mos tfrequent subtype, CMT1A, is associated with duplication of approximately 1.5 Mb fragment in 17p11-p12, that includes the PMP22 gene. OBJECTIVE: The aim of this study was to describe different strategies used for clinical and molecular CNT1A diagnoses among patients attending the National Rehabilitation Institute of Mexico (INR). MATERIAL AND METHODS: 17 patients had clinical and electrophysiological features compatible with CMT1. A molecular study using capillary electrophoresis (CE) was performed and a PMP22 gene duplication was detected RESULTS: Clinical, biochemical and electrophysiological studies constituted the inclusion criteria to establish a CMT1 diagnosis. With CE the duplication of the PMP22 gene was observable and we established a possible CMT1A diagnosis in seven patients. All duplications detected by capillary electrophoresis were corroborated using FISH. CONCLUSION: CE is a feasible and reliable method to detect PMP22 gene duplication. Using different clinical, electrophysiological and molecular strategies in this patient population allowed us to establish an accurate diagnosis and offer suitable genetic counseling.

Actualidad génetica y clínica en las polineuropatías sensoromotoras hereditarias / Genetic present time and clinic in thehereditary motor sensory polineuropathies

Como objetivo hemos tenido el ampliar el conocimiento en el tema de las polineuropatías sensorimotoras hereditarias y mostrar los aportes de la genética molecular en la clasificación de esta enfermedad. En el desarrollo, revisamos el tema de las polineuropatías sensorimotoras hereditarias partiendo desde sus primeras descripciones. Se hace énfasis en la generalidad del cuadro clínico, seleccionando inicialmente la clasificación de Dyck & Lambert para luego detallar el gran paso generado por los avances de la genética molecular en la clasificación exacta de este grupo de desórdenes de los nervios periféricos. Se establece como regla para clasificarlo la naturaleza de la polineuropatía, dividiéndola en Desmielinizante y Axonal. En cada uno de estos dos grupos se explica claramente el patrón de herencia (A. Dominante, A recesiva, Ligada al Cromosoma X) con sus respectivas mutaciones y productos proteicos alterados.Las neuropatías sensorimotoras son un gran síndrome, en el cual la existencia de múltiples mutaciones explica la gran variabilidad en el cuadro clínico y en la expresión de esta enfermedad. El diagnóstico exacto de estas neuropatías parece estar muy ligado a la genética molecular, por lo que la clasificación de Dyck y Lambert es la de mayor utilidad para una correcta interpretación clínica de este síndrome

Síndrome de Charcot-Marie-Tooth: a propósito de un caso clínico / Syndrome Charcot-Marie-Tooth disease: a purpose of a case

Los estudios del Síndrome de Charcot-Marie-Tooth (CMT) presenta heterogeneidad genética. Los estudios de conducción nerviosa y la práctica de biopsia de nervio periférico han permitido establecer dos tipos: CMT1: es hipertrófica, desmielinizante con descenso de las velocidades de conducción nerviosa motora. CMT2: velocidades de conducción nerviosa periférica normales o mínimamente descendidas y atrofia axonal primaria con mínima afectación de la mielina. Prevalencia entre 15 a 20 casos por 100.000 habitantes. Afecta a ambos sexos con ligera preferencia por los varones. Las características clínicas de CMT1 incluyen debilidad distal, atrofia de inicio en musculatura peroneal con extensión a dedos de las manos, hipo o arreflexia, pies cavos, engrosamiento de los nervios y alteraciones sensitivas distales. CMT2 es semejante al CMT1 aunque su inicio suele ser algo más tardío. Paciente escolar masculino de doce años, quien inicia cuadro clínico a los tres años caracterizado por tropiezos caídas frecuentes, dificultad para subir y bajar escaleras, y debilidad muscular de miembros inferiores de forma progresiva hasta la actualidad. Examen físico: marcha de estepaje, pie caído, hipotrofia de músculos intrapatelares bilaterales a predominio izquierdo, hiporreflexia y arreflexia en algunos grupos musculares y disminución de la fuerza muscular. Se realizó electromiografía y velocidad de conducción nerviosa siendo alteradas compatible junto a la clínica con CMT1. En conclusión es una patología que amerita el suficiente conocimiento por parte de los médicos en general para su correcto diagnóstico y manejo.

Genetics of hereditary motor and sensory neuropathy and the Costa Rican contribution: [review]

Hereditary motor and sensory neuropathy (HMSN) or Charcot-Marie-Tooth disease (CMT) is the most common hereditary illness of the peripheral nervous system. The genetics and the physiopathological aspects of the disease clarified until know, are here summarized. More than twenty genes and ten additional loci have been related with HMSN. These findings contribute to understand the metabolism of peripheral nerves and give the basis for molecular diagnostics and future therapy. Several Costa Rican families with CMT have been identified, specially with axonal forms. Two families present mutations in the myelin protein zero gene (IMPZ). In addition, linkage have been found between the disease and locus 19q13.3 in an extended family, and a mutation segregating with the disease is present in a candidate gene of the critical interval. Costa Rica has several advantages for genetical studies, that can contribute importantly in the generation of knowledge in the neurogenetical field.

Hereditary neuropathy with liability to pressure palsies (HNPP) patients of Korean ancestry with chromosome 17p11.2-p12 deletion

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant inherited disorder characterized by recurrent pressure palsies. Most HNPP patients have a 1.5 mb deletion in chromosome 17p11.2-p12. The present study aimed at evaluating the deletion of the 17p11.2-p12 region in Korean subjects with families exhibiting HNPP phenotype, and to determine the clinical, electrophysiological and morphological aspects specifically associated with this deletion in HNPP patients. By genotyping six microsatellite markers (D17S921, D17S955, D17S1358, D17S839, D17S122 and D17S261), HNPP with the deletion was observed in 79% (19 of 24) of HNPP families. Nerve conduction studies were performed in 35 HNPP patients from these 19 families. The observed HNPP deletion frequency in Koreans is consistent with findings in other populations. Disease onset occurred at a significantly earlier age in patients with recurrent pressure palsies than in those with a single attack (P<0.01). Nerve conduction studies demonstrated diffuse mild to moderate slowing of nerve conduction velocities that were worse over the common entrapment sites, regardless of the clinical manifestations. A long duration of compound muscle action potentials without a conduction block or a temporal dispersion is a characteristic of this disease. A sural nerve biopsy with teasing was performed in four patients, and tomacula of the myelin sheath was found in 56.4%. Our findings appear to support the existence of a phenotype/genotype correlation in HNPP patients of Korean ancestry with the deletion, and suggest that HNPP patients with earlier symptom onset face an increased chance of having recurrent attacks.

Hereditary motor and sensory neuropathy with congenital glaucoma

We report three siblings of a family with hereditary motor and sensory plyneuropathy (HMSN) and buphthalmos. Eletrophysiological studies showed a demyelinating neuropathy and pathological findings showed severe loss of myelinated fibers (MF), thin myelin sheaths and myelin infoldings in a few remaining MF. The presumed mode of inheritance is autosomal recesive. This family probably represents an unique form of CMT4 that may be related to one of the congenital glaucoma genic locus, particularly GLC3A and GLC3B, described in Turkish families.

Doença de Charcot-Marie-Tooth / Charcot-Marie-Tooth disease

A doença de Charcot-Marie-Tooth (CMT) é a mais frequente das doenças neuromusculares hereditárias. Várias casuísticas mundiais confirmam esta alta prevalência. O tipo I (desmielinizante) é mais frequente do que o tipo II (axonal), porém em alguns países esta relaçäo se inverte. Além da herança autossômica dominante (mais comum) e da autossômica recessiva há famílias de hereditariedade ligada ao cromossomo X, dominante ou recessiva. Recentemente verificou-se que a maoiria das famílias de doença de CMT I dominante está ligada ao cromossomo 17; algumas poucas famílias têm ligaçäo com o cromossomo I e em algumas näo se descobriu a ligaçäo cromossômica. Apesar do tipo I ser desmielinizante alguns pensam estar a lesäo inicial no axônio. Entretando, parece que há uma alteraçäo da proteína PMP22 mapeada na regiäo da duplicaçäo da doença de CMT I. Este gen seria responsável por desencadeamento da desmielinizaçäo e remielinizaçäo deste tipo de doença

Doença de Charcot-Marie-Tooth: estudo de 45 pacientes / Charcot-Marie-Tooth disease: study of 45 patients

A doença de Chacot-Marie-Tooth (CMT) é uma das moléstias mais frequentes do sistema nervoso periférico e ocupa o primeiro lugar dentre as afecções neuromusculares hereditárias. Estudamos 45 pacientes com a doença de CMT atendidos no Hospital Universitário Antônio Pedro da Universidade Federal Fluminense. Todos foram submetidos a estudos de neurocondução e quase todos à biopsia do nervo sural. Onze enfermos pertenciam ao tipo I e 34 ao tipo II da doença CMT. Vinte e três tinham herança do tipo autossômico, sete casos do tipo autossômico recessivo e 15 não tinham antecedentes familiares da doença...Os achados de biópsia do nervo sural em microscopia óptica e eletrônica foram semelhantes aos até hoje descritos. Em um caso do tipo I verificou-se atrofia axonal, indicando que a afecção, na realidade, tem origem no axônio. Nos casos do tipo I e II não houve concordância do quadro clínico com os achados da neurocondução, nem com os dados anatomopatológicos. No tipo I existiu paralelismo entre a neurocondução e os achados de biópsia do nervo. Nos casos do tipo II não houve relação das alterações da neurocondução com os achados anatomopatológicos do nervo sural. Considerando as latências e as amplitudes do nervo sural, houve relação de alteração das mesmas com os dados de biópsia nervoso em ambos tipos da doença de CMTA