Clinical, pathological and genetic characteristics of 8 patients with distal hereditary motor neuropathy / 北京大学学报(医学版)

OBJECTIVE@#Distal hereditary motor neuropathy (dHMN) comprises a heterogeneous group of inherited disorders associated with neurodegeneration of motor nerves and neurons, mainly charac-terized by progressive atrophy and weakness of distal muscle without clinical or electrophysiological sensory abnormalities. To improve the recognition and diagnosis of the disease, we summarized the clinical manifestations, electrophysiological, pathological, and genetic characteristics in eight patients with dHMN.@*METHODS@#Eight probands from different families diagnosed with dHMN were recruited in this study between June 2018 and April 2019 at Peking University People's Hospital. Eight patients underwent complete neurological examination and standard electrophysiological examinations. The clinical criteria were consistent with the patients presenting with a pure motor neuropathy with no sensory changes on electrophysiology. The detailed clinical symptoms, neurophysiological examinations, pathological features and gene mutations were analyzed retrospectively. Genetic testing was performed on the eight patients using targeted next-generation sequencing panel for inherited neuromuscular disorder and was combined with segregation analysis.@*RESULTS@#The age of onset ranged between 11 and 64 years (median 39.5 years) in our dHMN patients. All the cases showed a slowly progressive disease course, mainly characterized by distal limb muscle weakness and atrophy. The motor nerve conduction revealed decreased compound muscle action potential amplitude and velocity, while the sensory nerve conduction velocities and action potentials were not affected. Needle electromyography indicated neurogenic chronic denervation in all patients. Muscle biopsy performed in two patients demonstrated neurogenic skeletal muscle damage. Sural nerve biopsy was performed in one patient, Semithin sections shows relatively normal density and structure of large myelinated fibers, except very few fibers with thin myelin sheaths, which suggested very mild sensory nerve involvement. Eight different genes known to be associated with dHMN were identified in the patients by next-generation sequencing, pathogenic dHMN mutations were identified in three genes, and the detection rate of confirmed genetic diagnosis of dHMN was 37.5% (3/8). Whereas five variants of uncertain significance (VUS) were identified, among which two novel variants co-segregated the phenotype.@*CONCLUSION@#dHMN is a group of inherited peripheral neuropathies with great clinical and genetic heterogeneity. Next-generation sequencing is widely used to discover pathogenic genes in patients with dHMN, but more than half of the patients still remain genetically unknown.

Neuropatía motora multifocal: reporte de un caso / Multifocal motor neuropathy: a case report

Las neuropatías agrupan un gran número de patologías de nervio periférico; estas pueden ser adquiridas o hereditarias, de origen sistémico o restringidas a un número de nervios. Las neuropatías son causa de dolor e incapacidad y requieren un manejo multidisciplinar para mejorar la calidad de vida de los pacientes. Dentro de ellas tenemos la neuropatía motora multifocal (NMM), también denominada 'neuropatía motora multifocal con bloqueo de conducción' (NMMCB), la cual es una neuropatía adquirida, inflamatoria, poco frecuente, caracterizada por debilidad en las extremidades, sin pérdida sensorial, progresiva y asimétrica. Se presenta además un bloqueo persistente de la conducción nerviosa que afecta las fibras motoras de forma selectiva.

Neuropathies group a large number of peripheral nerve pathologies; these can be acquired or hereditary, of systemic origin or restricted to a number of nerves. Neuropathies cause pain and disability and require multidisciplinary management to improve the quality of life of patients. Among them we have multifocal motor neuropathy (MMN), also called 'multifocal motor neuropathy with conduction block' (MMPNB), which is an acquired, inflammatory, rare neuropathy, characterized by weakness in the extremities, without sensory loss, progressive and asymmetric. There is also a persistent nerve conduction block that selectively affects motor fibers.

Neuropatía sensitiva y motora hereditaria: Enfermedad de Charcot Marie Tooth / Hereditary Motor and Sensory Neuropathy: Charcot Marie Tooth disease

La enfermedad de Charcot Marie Tooth (ECMT) o neuropatía sensitiva y motora hereditaria es el grupo de trastornos degenerativos más común del sistema nervioso periférico, asociado a un conjunto de alteraciones genéticas que cambia la estructura, formación y mantenimiento de la mielina. Afecta a 1 de cada 2500 personas sin guardar relación con la edad, género o etnia; su etiología es únicamente genética. Según la velocidad de conducción nerviosa se clasifca en desmielinizante o CMT1, axonal o CMT2 e intermedia la misma que posee características de los dos anteriores. La ECMT en la mayoría de los casos es una enfermedad lentamente progresiva, se presenta con signos característicos de pie cavo, pierna de cigüeña, atrofa y disminución de la fuerza muscular, alteración en la percepción de estímulos vibratorios, de comienzo distal con progresión a proximal; arreflexia y alteración de la marcha. El diagnóstico se realiza en base a los antecedentes familiares, clínica y examen físico, complementando con estudios electromiográfcos para determinar su clasifcación. Las pruebas genéticas se deben realizar dependiendo al tipo de ECMT en sospecha, las mismas que servirán para realizar consejería familiar. En la actualidad no existe tratamiento específco ni curativo, por lo que se debe brindar apoyo con terapia física y de rehabilitación, psicológica, ocupacional, así como un manejo óptimo del dolor.

Charcot Mariet Tooth's disease (ECMT) or hereditary sensory and motor neuropathy is the one of the most common group of degenerative disorders of the peripheral nervous system, related with a set of genetic alterations that changes the structure, formation and maintenance of myelin. It affects 1 out of 2500 people without considering the age, gender or ethnicity; its etiology is entirely genetic. According to the nerve conduction velocity it is classifed in demyelinating or CMT1, axonal or CMT2 and intermediate the same that has the features of the two previous ones. ECMT in majority of cases it is a slowly progressive disease, presenting with characteristic signs of high instep, stork leg, atrophy and decreased muscle strength, altered perception of vibratory stimuli, distal beginning with proximal progression; arreflexia and alteration of march. The diagnosis is based on family history, clinical and physical examination, complemented by electromyography studies, to determine their classifcation. Genetic tests are taken, based on the type of suspected ECMT, and these will be used for family counseling. Nowadays there is no specifc and curative treatment, that's why support should be provided with physical and rehabilitation therapies, psychological, occupational, as well as an optimal pain control.

Progress of clinical and genetic research on distal hereditary motor neuropathy / 中华医学遗传学杂志

Distal hereditary motor neuropathy (dHMN) is a group of clinically and genetically heterogeneous disorders characterized by progressive distal weakness and atrophy. The onset of dHMN is at mid-adulthood or early childhood, and the symptoms are mainly present in the lower limbs. Besides weakness and atrophy of distal limb muscles, some patients may develop bulbar paralysis, and some may also present with mild sensory disturbance. Decreased or absent tendon reflexes may be discovered. Electromyography may show neurogenic damages. Muscular biopsy may reveal neurogenic amyotrophy. An increasing number of genes have been associated with dHMN. Pathogenesis of dHMN may include formation of protein aggregates, impairment of autophagy pathway, RNA processing, translation synthesis, axonal transport, endoplasmic reticulum stress, calcium channel and neuroprotection. A review for recent progress made on clinical characterization and molecular genetics of dHMN is provided.

Funcionamiento Cognitivo Global y Conducta Adaptativa en dos Niñas con Neuropatía Sensitiva Autonómica Hereditaria Tipo IV / Global cognitive and adaptive functioning in two girls with hereditary sensory and autonomic neuropathy type IV

La neuropatía sensitiva autonómica hereditaria tipo IV (HSAN-IV) es una condición neurológica de origen genético extremadamente rara que puede cursar con discapacidad intelectual, sin embargo, hay escasas publicaciones sobre las características del funcionamiento cognitivo global y la conducta adaptativa de los afectados. En este estudio se describe la capacidad cognitiva global y el funcionamiento adaptativo de dos niñas de 12 y 14 años diagnosticadas con HSANIV, incluyendo una caracterización de los procesos de comprensión verbal, razonamiento perceptual, memoria de trabajo y velocidad de procesamiento. Las menores fueron evaluadas mediante la Escala de Inteligencia para niños de Wechsler cuarta edición (WISC-IV) encontrándose en ambos casos un bajo índice de comprensión verbal, una medida del desarrollo cognitivo alcanzado a través de la historia de aprendizaje de las niñas; así como un bajo índice de razonamiento perceptivo, indicador de su capacidad para adaptarse y afrontar situaciones nuevas de forma flexible. Esto se acompaña de dificultad en la manipulación de información en la memoria para la resolución de problemas y enlentecimiento en la velocidad de procesamiento de la información. Adicionalmente, se evaluó su funcionamiento adaptativo mediante el sistema de evaluación de la conducta adaptativa ABAS-II, el cual se caracterizó por fortalezas en habilidades comunicativas, uso de recursos comunitarios y vida en el hogar; con limitaciones en habilidades académicas y de autocuidado. En conclusión, la HSAN-IV es una condición que cursa con discapacidad intelectual con necesidades de apoyo variables en intensidad. En los casos estudiados se encontró discapacidad intelectual con necesidad de apoyo limitado, es decir, los apoyos se requieren de forma regular durante un periodo de tiempo corto pero definido.

Hereditary sensory autonomic neuropathy type IV (HSAN-IV) is a neurological condition of extremely rare genetic origin that may be associated with intellectual disability; however, there are few publications about the characteristics of global cognitive functioning and adaptive behaviour of these patients. In this study we describe the global cognitive function and the adaptive behavior of two girls aged 12 and 14 diagnosed with HSAN-IV, including a characterization of the processes of verbal comprehension, perceptual reasoning, working memory and processing speed. The children were assessed using the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV), finding in both cases a low level of verbal comprehension, a measure of cognitive development achieved through the girls' learning history; as well as a low rate of perceptual reasoning, indicator of their ability to adapt and face new situations in a flexible way. This is accompanied by difficulty in manipulating information in the memory to solve problems and slow down the speed of information processing. Additionally, its adaptive functioning was evaluated through the Adaptive Behavior Assessment System ABAS-II, which was characterized by strengths in communication skills, use of community resources and life at home; with limitations in academic and self-care skills. In conclusion, HSAN-IV is a condition related with intellectual disability with varying support needs in intensity. In the cases studied, intellectual disability was found with limited need for support, that is, supports are required on a regular basis for a short but defined period.

Enfermedad de Charcot-Marie-Tooth en numerosos miembros de una familia / Charcot-Marie-Tooth disease in several members of a family

La enfermedad de Charcot-Marie-Tooth es una afección degenerativa del sistema nervioso periférico, que presenta gran heterogeneidad genética y clínica. La presentación con patrón autosómico dominante, conocida en algunas clasificaciones como de tipo 1, es la más frecuente; asimismo, la confección del árbol genealógico resulta ser el instrumento de mayor importancia para conocer el tipo de herencia. A tales efectos, se describen 2 casos clínicos pertenecientes a una familia con 35 miembros afectados por este trastorno neurológico, atendidos en el Centro Provincial de Genética Médica de Santiago de Cuba.

Charcot-Marie-Tooth disease is a degenerative affection of the peripheral nervous system that presents great genetic and clinic heterogeneity. The presentation with autosomal dominant pattern, well-known in some classifications as type I, is the most frequent; also, the making of the genealogical tree turns out to be the most important instrument to know the inheritance type. To such effects, 2 case reports belonging to a family with 35 members affected by this neurological dysfunction are described, assisted in the Provincial Center of Medical Genetics in Santiago de Cuba.

Analysis of the clinical, electrophysiological and genetic features of a family affected with hereditary neuropathy with liability to pressure palsies / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To delineate the clinical, electrophysiological and genetics features of a family where 4 members were affected with hereditary neuropathy with liability to pressure palsies (HNPP).</p><p><b>METHODS</b>Clinical features of the 4 patients were summarized. Electrophysiological examination and genetic analysis were carried out.</p><p><b>RESULTS</b>All of the patients showed recurrent motor and sensory disturbances after minor traction or constriction. Electrophysiology study revealed that the prolonged latency and reduced conduction velocity of peripheral nerve were general and with multiple sites of affection. The nerve locations liable to entrapment showed conduction block. A deletion mutation of peripheral myelin protein 22 (PMP22) gene was identified by genetic analysis.</p><p><b>CONCLUSION</b>HNPP usually affects areas where nerves are liable to entrapment, and presents with motor and sensory disturbances of the innervated areas. Electrophysiological study reveals general nervous demyelination. Genetic analysis can clarify the diagnosis of HNPP.</p>

Novel Compound Heterozygous Nonsense PRX Mutations in a Korean Dejerine-Sottas Neuropathy Family

BACKGROUND: Mutations in the gene encoding periaxin (PRX) are known to cause autosomal recessive Dejerine-Sottas neuropathy (DSN) or Charcot-Marie-Tooth disease type 4F. However, there have been no reports describing Korean patients with these mutations. CASE REPORT: We examined a Korean DSN patient with an early-onset, slowly progressive, demyelinating neuropathy with prominent sensory involvement. Whole-exome sequencing and subsequent capillary sequencing revealed novel compound heterozygous nonsense mutations (p.R392X and p.R679X) in PRX. One mutation was transmitted from each of the patient's parents. No unaffected family member had both mutations, and the mutations were not found in healthy controls. CONCLUSIONS: We believe that these novel compound heterozygous nonsense mutations are the underlying cause of DSN. The clinical, electrophysiologic, and pathologic phenotypes in this family were similar to those described previously for patients with PRX mutations. We have identified the first PRX mutation in a Korean patient with DSN.

Dynamic Transcriptional Events in Distal Sural Nerve Revealed by Transcriptome Analysis

Compared with biochemical information available about the diseases in the central nervous system, that for peripheral neuropathy is quite limited primarily due to the difficulties in obtaining samples. Characterization of the core pathology is a prerequisite to the development of personalized medicine for genetically heterogeneous diseases, such as hereditary motor and sensory neuropathy (HMSN). Here, we first documented the transcriptome profile of distal sural nerve obtained from HMSN patients. RNA-seq analysis revealed that over 12,000 genes are expressed in distal sural nerve. Among them 4,000 transcripts are novel and 10 fusion genes per sample were observed. Comparing dataset from whole exome sequencing revealed that over 1,500 transcriptional base modifications occur during transcription. These data implicate that dynamic alterations are generated when genetic information are transitioned in distal sural nerve. Although, we could not find significant alterations associated with HMSN, these data might provide crucial information about the pathophysiology of HMSN. Therefore, next step in the development of therapeutic strategy for HMSN might be unveiling biochemical and biophysical abnormalities derived from those potent variation.

Hereditary Motor and Sensory Neuropathy Type VI with Bilateral Middle Cerebellar Peduncle Involvement

Charcot-Marie-Tooth disease (CMT) 2A with optic atrophy is referred to as hereditary motor and sensory neuropathy type VI (HMSN VI) and is caused by mitofusin 2 gene (MFN2) mutation. In patients with MFN2 related CMT, central nervous system is known to be also involved and cerebral white matter is mostly involved. We report a patient confirmed as HMSN VI who had isolated bilateral middle cerebellar peduncular lesions in brain MRI.

Estudo da emissão de luz por diodoinfravermelho na dor neuropática em ratos / Study of infrared light emitting diodes infraredon neuropathic pain in rats

Introdução: A lesão nervosa periférica pode causar alteraçõesfuncionais tanto sensitivas quanto motoras, podendo promoverimportantes comprometimentos, especialmente a dor neuropática.Dentre os vários tratamentos propostos está o emprego da luz monocromáticade baixa intensidade, como o diodo de emissão de luz(LED). Objetivo: Avaliar o efeito analgésico do LED no espectroinfravermelho em modelo experimental de dor neuropática porconstrição do nervo ciático em ratos. Material e métodos: Foramutilizados 24 ratos machos Wistar, randomizados em 4 grupos (n =6). Grupo I: animais neuropáticos e tratados com LED; grupo II:animais neuropáticos e tratados com o LED desligado (placebo);grupo III: animais Sham e tratados com LED; grupo IV: animaisSham e tratados com LED desligado (placebo). Para avaliar a eficáciado tratamento, foram empregados parâmetros de nocicepção comoalodínia mecânica estática, dinâmica e térmica ao frio; hiperalgesiatérmica ao calor e nocicepção espontânea. Resultados: Os animaisneuropáticos desenvolveram alodínia e hiperalgesia ao estímulomecânico, térmico e nocicepção espontânea em 7 dias (Tempo 0)contados a partir da indução da neuropatia, mantendo essas manifestaçõesaté o 14º dia. Conclusão: O tratamento contínuo com LED noespectro infravermelho promoveu efeito analgésico em um modeloexperimental de dor neuropática em ratos. Os resultados obtidosneste estudo sugerem que esse recurso físico pode ser utilizado notratamento de pacientes com dor neuropática.

Introduction: The peripheral nerve injury can cause sensory andmotor functional changes, promoting important damages, especiallyneuropathic pain. The use of monochromatic light of low intensity,such as light-emitting diode (LED) is among different treatmentsoptions. Objective: This study proposes an evaluation of analgesiceffect of LED in the infrared spectrum in experimental model ofneuropathic pain induced by constriction of the sciatic nerve in rats.Methods: We used 24 male Wistar rats randomized into 4 groups (n= 6). Group I: neuropathic animals, treated with LED; group II:neuropathic animals, treated with LED (placebo); group III: Shamanimals treated with LED, group IV: Sham animals treated withLED turned off (placebo). We used nociception parameters suchas static mechanical allodynia, thermal (cold) dynamics, thermal(heat) hyperalgesia and spontaneous nociceptive in order to evaluatetreatment efficacy. Results: All animals developed neuropathicallodynia and hyperalgesia to mechanical stimulation, thermal andspontaneous nociception in 7 days (time 0), starting on inductionof neuropathy, maintaining these conditions until the 14th day.Conclusion: Continuous LED treatment with infrared spectrumpromotes analgesic effect in experimental model of neuropathic painin rats. The results of this study suggest that this treatment may beused to treat patients with neuropathic pain.

Neuropatía hereditaria con susceptibilidad a la parálisis por presión: importancia del protocolo electrodiagnóstico / Hereditary neuropathy with liability to pressure palsies. Importance of electrodiagnostic protocol

Introduction: Hereditary neuropathy with susceptibility to pressure palsy is a genetic disorder of autosomal dominant inheritance that affects mainly the peripheral nerve myelin. This work aims to give a detailed description of a peculiar case and a literature review. Method: Neurophysiological and genetic study of 21 years old patient referred to the Clinical Neurophysiology Unit, by paresthesia in the right ulnar nerve territory. Results: Electromyographic examination demonstrated the existence of a sensory-motor polineuropathy greater intensity in multiple locations susceptible to nerve entrapment and genetic study confirmed the existence of a deletion at the PMP22 gene (chromosome 17p11.2). Conclusions: Hereditary neuropathy with susceptibility to pressure palsy is an underdiagnosed disease that may go unnoticed by simulating a simple compressive neuropathy. A rigorous neurophysiological study is essential to carry out a suspected diagnosis and to guide subsequent genetic diagnosis.

Introducción: La neuropatía hereditaria con susceptibilidad a la parálisis por presión es un trastorno genético de herencia autosómica dominante que afecta principalmente a la mielina de los nervios periféricos. Con este trabajo se pretende por un lado hacer una descripción detallada de un caso peculiar resaltando la importancia del protocolo electrodiagnóstico además de realizar una revisión bibliográfica sobre el tema. Método: Estudio neurofisiológico y genético de paciente de 21 años remitido a la Unidad de Neurofisiología Clínica por parestesias en territorio del nervio cubital derecho. Resultados: La exploración electromiográfica objetivó la existencia de una polineuropatía sensitivo-motora de predominio desmielinizante y mayor intensidad en localizaciones susceptibles al atrapamiento nervioso y el estudio genético confirmó la existencia de una deleción a nivel del gen PMP22 (cromosoma 17p11.2). Conclusiones: La neuropatía hereditaria con susceptibilidad a la parálisis por presión es una enfermedad infradiagnosticada que puede pasar desapercibida simulando una simple neuropatía compresiva. Un riguroso estudio neurofisiológico es fundamental para llevar a cabo un diagnóstico de sospecha así como para orientar el posterior diagnóstico genético.

Neuropatía auditiva, diagnóstico y manejo audiológico / Auditory neuropathy / dyssychrony, assessment and audiologic management

Los hallazgos clínicos que definen una neuropatía/des sincronía (NA/DA) son la integridad de las células ciliadas evidenciado, mediante la presencia de emisiones otoacústicas evocadas (EOAe) y/o la presencia de potenciales microfónicos cocleares (PMIC), junto con la ausencia de actividad neural evocada a nivel del VIII par craneano (potencial de acción compuesto) y tronco cerebral (potencial evocado auditivo de tronco (PEAT)). Las condiciones clínicas relacionadas con una NA/DA incluyen a la hiperbilirrubinemia, enfermedades neurovegetativas (ejemplo ataxia de Friedreich), síndrome de Charcot-Marie-Tooth así como otras neuropatías sensoriomotoras, desórdenes mitocondriales y neuropatías isquémica-hipóxicas como resultados de asfixia. El desarrollo de las habilidades auditivas y comunicacionales pueden estar comprometidas en forma importante en los niños con aparición prelingual de una NA/DA, mayor es aún este compromiso al no existir un perfil pronóstico preestablecido del desarrollo y resultados en el tratamiento de este desorden. En la actualidad existen múltiples estudios en donde se ha observado que hasta 50 por ciento de los pacientes con NA/DA presentan algún grado de beneficio al usar audífonos por lo que se sugiere que sistemas de amplificación como los audífonos o incluso implante coclear deberían ser el primer paso en el proceso de (re)habilitación.

The clinical findings that define an auditory neuropathy/dyssynchrony (AN/Dys) are the integrity of the outer hair cells demonstrated by the presence of evoked otoacoustics emissions (OAEe) and/or the presence of cochlear microphonic potential (CMP) along with the absence of neural activity evoked at level of VIII nerve (action potential compound) and brainstem (Auditory Brainstem Response, ABR). The clinical conditions related to an AN they include hiperbilirrubinemia, neurodegenerative diseases (eg ataxia of Friedreich), Charcot-Marie-Tooth syndrome as well as other sensoriomotor neuropathies, mitocondrial disorders and hypoxic neuropathy as perinatal asphyxia. The development of the auditory and communicational abilities can be compromise in children with prelingual onset of an AN/Dys, the development and results of treatment of this disorder is still this commitment when not existing a profile prognosis. At the present time multiple studies have been observed that until a 50 percent of the patients with AN present some degree of benefit using hearing aids, reason why it suggests amplification systems as the hearing aids or even cochlear implant would have to be the first step in the process of (re) habilitation of these patients.

Autosomal dominant HMSN with proximal involvement: new Brazilian cases / HMSN autossômica dominante com envolvimento proximal: novos casos brasileiros

We report four Brazilian siblings with Autosomal Dominant Hereditary Motor Sensory Neuropathy with Proximal Dominant Involvement (HMSN-P), a rare form of HMSN, that was characterized by proximal dominant muscle weakness and atrophy onset after the age of 30 years, fasciculation, arreflexia and sensory disturbances with autosomal dominant inheritance. Electrophysiological study and sural nerve biopsy were in the accordance with axonal sensory motor polyneuropathy and laboratorial analysis disclosed serum lipids and muscle enzymes abnormalities. Our report is the first done by a group outside Japan, where the disease initially seemed to be restricted and stressed the phenotypic variability from the original report.

Relatamos os casos de quatro irmãos brasileiros com Neuropatia Sensitivo Motora Hereditária com Envolvimento Proximal Dominante (HMSN-P), uma forma rara de HMSN caracterizada por fraqueza muscular de predomínio proximal e atrofia de instalação após os 30 anos, fasciculações, arreflexia, distúrbios sensitivos e padrão de herança autossômica dominante. Os estudos eletrofisiológicos e de biópsia do nervo sural confirmaram o diagnóstico de polineuropatia sensitivo-motora com padrão lesional axonal. Laboratorialmente foram constatadas anormalidades séricas no metabolismo lipídico e enzimas musculares. Nosso relato é o primeiro feito por um grupo fora do Japão, onde a doença parecia restrita até então e ressalta a variabilidade fenotípica apresentada nos casos Brasileiros.

Genetics of Hereditary Peripheral Neuropathies

Hereditary peripheral neuropathies can be categorized as hereditary motor and sensory neuropathies (HMSN), hereditary motor neuropathies (HMN), and hereditary sensory neuropathies (HSN). HMSN, HMN, and HSN are further subdivided into several subtypes. Here, we review the most recent findings in the molecular diagnosis and therapeutic strategy for hereditary peripheral neuropathies. The products of genes associated with hereditary peripheral neuropathy phenotypes are important for neuronal structure maintenance, axonal transport, nerve signal transduction, and functions related to the cellular integrity. Identifying the molecular basis of hereditary peripheral neuropathy and studying the relevant genes and their functions is important to understand the pathophysiological mechanisms of these neurodegenerative disorders, as well as the processes involved in the normal development and function of the peripheral nervous system. These advances and the better understanding of the pathogenesis of peripheral neuropathies represent a challenge for the diagnoses and managements of hereditary peripheral neuropathy patients in developing future supportive and curative therapies.

Neuropatía hereditaria con predisposición a la parálisis por compresión: presentación de casos clínicos y electrofisiológicos / Hereditary neuropathy with liability to pressure palsies: presentation of clinical and electrophysiological cases

Hereditary neuropathy with liability to pressure palsies (HNPP) is a rare autosomal dominant neuropathy characterized by recurrent episodes of painless multiple nerve entrapments. We present five cases of HNPP confirmed by clinical and electrophysiological studies. Genetic confirmation of the diagnosis was performed in only one of the cases, given the fact that there are no laboratories performing this test inChile. This emphasizes the importance of electrophysiological diagnostic suspicion and the need for electrophysiological studies in family members even when asymptomatic.

Neuropatía del nervio pudendo post parto vaginal / Pudend Nerv neuropaty postparto vaginal

Se presenta un caso de neuropatía del nervio pudendo, pos parto vaginal en una paciente segundigesta de 30 años, por­tadora de un síndrome muy raro (NPV). La sintomatología mas importante es el dolor perineal que puede asociarse a disfuncion urinaria, anal e incluso sexual; para el diagnostico es importante utilizar dos criteros mayores, o un criterio mayor y dos criterios menores y el tratamiento debe ser siempre secuencial e incluir tres etapas.

We present a pudend nerve neuropathy, pos parto vaginal case in a 30 year old secondgest, carried of a very strange sindrome (NPV). The most important synthomwas perineal pain which can be asociated qith urinary disfunction or even sexual diosfunction; for the diagnosis is important to use two major criterias or una major criteria and two lesser criterias, and the tratment must always be secuencial and must include three stages.

Impacto de programa fisioterapêutico no desempenho funcional da criança com doença de Charcot-Marie-Tooth tipo 2: estudo de caso / Impact of a physical therapy program on the functional performance of a child with Charcot-Marie-Tooth disease type 2: a case report

O estudo visou verificar a influência de um programa fisioterapêutico no desempenho funcional de uma criança com diagnóstico de Doenca de Charcot-Marie-Tooth tipo 2. O participante (sexo masculino, 6 anos) apresentava comprometimento motor e sensitivo em membros superiores e inferiores...

This case study aimed at verifying then influence of a physical therapy program on the functional performance of a child with diagnosis of Charcot-Marie-Tooth disease type 2. The 6 year-old male child presented low and upper limbs affected at both motor and sensitive levels...