RESUMEN
Both the myotonic dystrophy type 1 (DM1) and the X-linked dominant Charcot-Marie-Tooth disease (CMTX1) are well-established inherited neuromuscular disorders characterized by progressive weakness and atrophy of the distal limb muscles. The underlying causes of the DM1 and CMTX1 are mutations in the DMPK and GJB1 gene, respectively. A patient with both DM1 and CMTX1 inherited these from his father and mother, respectively. Histopathological and electrodiagnostic studies revealed both chronic neuropathic and myopathic features. Physical disabilities were more severe than seen with either DM1 or CMTX1 alone. In addition, the present case reveals an asymmetric atrophy (22%) of the right calf muscle compared to the left side.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth/genética , Cromosomas Humanos X , Genes Dominantes , Distrofia Miotónica/genética , Secuencia de Aminoácidos , Secuencia de Bases , Estudios de Casos y Controles , Electrofisiología/métodos , Salud de la Familia , Humanos , Masculino , Datos de Secuencia Molecular , Músculo Esquelético/patología , Mutación , Linaje , Análisis de Secuencia de ADNRESUMEN
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 alpha-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.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth/genética , Predisposición Genética a la Enfermedad , Péptidos y Proteínas de Señalización Intracelular/genética , Mutación Missense , Proteínas Serina-Treonina Quinasas/genética , Adolescente , Adulto , Edad de Inicio , Animales , Pueblo Asiatico , Enfermedad de Charcot-Marie-Tooth/diagnóstico por imagen , Enfermedad de Charcot-Marie-Tooth/fisiopatología , Niño , Preescolar , Femenino , Humanos , Corea (Geográfico) , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Atrofia Muscular/diagnóstico por imagen , Atrofia Muscular/fisiopatología , Conducción Nerviosa/genética , Linaje , Cintigrafía , alfa-Cristalinas/genéticaRESUMEN
OBJECTIVE: To investigate the characteristics of foot deformities in patients with Charcot-Marie-Tooth (CMT) disease compared with normal persons according to severity of disease. METHOD: Sixty-two patients with CMT disease were recruited for this study. The normal control group was composed of 28 healthy people without any foot deformity. Patients were classified into a mild group and a moderate group according to the CMT neuropathy score. Ten typical radiological angles representing foot deformities such as pes equinus and pes varus were measured. The CMT group angles were compared with those of the normal control group, and those of the mild group were also compared with those of the moderate group. RESULTS: The lateral (Lat.) talo-first metatarsal angle, anteroposterior talo-first metatarsal angle, Lat. calcaneal-first metatarsal angle, Lat. naviocuboid overlap, Lat. calcaneal pitch, Lat. tibiocalcaneal angle, and Lat. talocalcaneal angle in the CMT group showed a significant difference compared to the normal control group (p<0.05). These findings revealed CMT patients have pes cavus, forefoot adduction, midfoot supination and pes varus deformity. Compared to the mild group, the moderate group significantly showed an increased Lat. calcaneal pitch and decreased Lat. calcaneal-first metatarsal angle, Lat. tibiocalcaneal angle, Lat. talocalcaneal angle, and Lat. talo-first metatarsal angle (p<0.05). These findings revealed that the pes cavus deformity of CMT patients tend to be worse with disease severity. CONCLUSION: The characteristic equinovarus foot deformity patterns in CMT patients were revealed and these deformities tended to be worse with disease severity. Radiographic measures may be useful for the investigation of foot deformities in CMT patients.
RESUMEN
A wide range of phenotypes have been reported in autosomal recessive (AR) Charcot-Marie-Tooth disease (CMT) patients carrying mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene, such as axonal, demyelinating, and intermediate forms of AR CMT. There have been very few reports of GDAP1 mutations in autosomal dominant (AD) CMT. Here, we report an AD CMT family with a novel Q218E mutation in the GDAP1 gene. The mutation was located within the well-conserved glutathione S-transferase (GST) core region and co-segregated with the affected members in the pedigree. The affected AD CMT individuals had a later disease onset and much milder phenotypes than the AR CMT patients, and the histopathologic examination revealed both axonal degeneration and demyelination.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth/genética , Proteínas del Tejido Nervioso/genética , Mutación Puntual/genética , Adolescente , Secuencia de Aminoácidos , Secuencia de Bases , Enfermedad de Charcot-Marie-Tooth/patología , Análisis Mutacional de ADN , Electrofisiología , Femenino , Genes Dominantes/genética , Humanos , Corea (Geográfico) , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Nervio Sural/ultraestructuraRESUMEN
Charcot-Marie-Tooth disease (CMT) is classified into demyelinating neuropathy (CMT1) and axonal neuropathy (CMT2). Mutations in the neurofilament light chain polypeptide (NEFL) gene are present in CMT2E and CMT1F neuropathies. Two types of Pro22 mutations have been previously reported: Pro22Ser in CMT2E with giant axons, and Pro22Thr in CMT1F. In this study, we identified another Pro22 mutation, Pro22Arg, in a Korean CMT1 family. An investigation to identify the clinical and pathological characteristics of the Pro22Arg revealed that it is associated with demyelinating neuropathy features in CMT1F. Histopathological findings showed onion bulb formations but no giant axons. It appears that the Pro22 mutations may influence not only the Thr-Pro phosphorylation site by proline-directed protein kinases but also other structural alteration of the NEFL protein in a different way.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth/genética , Mutación/genética , Proteínas de Neurofilamentos/genética , Adolescente , Adulto , Secuencia de Aminoácidos , Enfermedad de Charcot-Marie-Tooth/patología , Niño , Preescolar , Análisis Mutacional de ADN , Electrofisiología , Femenino , Genotipo , Humanos , Masculino , Datos de Secuencia Molecular , Linaje , Homología de Secuencia de AminoácidoRESUMEN
Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with duplication of chromosome 17p11.2-p12, whereas hereditary neuropathy with liability to pressure palsies (HNPP), which is an autosomal dominant neuropathy showing characteristics of recurrent pressure palsies, is associated with 17p11.2-p12 deletion. An altered gene dosage of PMP22 is believed to the main cause underlying the CMT1A and HNPP phenotypes. Although CMT1A and HNPP are associated with the same locus, there has been no report of these two mutations within a single family. We report a rare family harboring CMT1A duplication and HNPP deletion.