Intermediate conduction velocity in two cases of Charcot-Marie-Tooth disease type 1A.

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease type 1A (CMT1A) is the most prevalent hereditary neuropathy worldwide and classically has slow nerve conduction velocity (NCV), in most cases below 38 m/s. Two unrelated patients with motor NCVs in the upper limbs above 38 m/s are reported. METHOD: Case report. RESULTS: Two genetically confirmed CMT1A patients are presented, from two unrelated families (one of British origin and the other of Brazilian origin). Both individuals had upper limb motor NCVs above 38 m/s, with values ranging from 41.9 to 45 m/s in the median nerve and from 42 to 42.3 m/s in the ulnar nerve. They presented with a very mild phenotype, with CMT Neuropathy Score version 2 (CMTNSv2) of 6 and 5, respectively. In contrast, affected family members within both kinships exhibited a classical phenotype with more severe disease manifestation (CMTNSv2 ranging from 12 to 20) and motor NCVs below 30 m/s. CONCLUSION: These cases, although very rare, highlight the importance of testing PMP22 duplication in patients with intermediate conduction velocities.

[Genetic distribution in Chinese patients with hereditary peripheral neuropathy].

OBJECTIVE: To analyze the distribution characteristics of hereditary peripheral neuropathy (HPN) pathogenic genes in Chinese Han population, and to explore the potential pathogenesis and treatment prospects of HPN and related diseases. METHODS: Six hundred and fifty-six index patients with HPN were enrolled in Peking University Third Hospital and China-Japan Friendship Hospital from January 2007 to May 2022. The PMP22 duplication and deletion mutations were screened and validated by multiplex ligation probe amplification technique. The next-generation sequencing gene panel or whole exome sequencing was used, and the suspected genes were validated by Sanger sequencing. RESULTS: Charcot-Marie-Tooth (CMT) accounted for 74.3% (495/666) of the patients with HPN, of whom 69.1% (342/495) were genetically confirmed. The most common genes of CMT were PMP22 duplication, MFN2 and GJB1 mutations, which accounted for 71.3% (244/342) of the patients with genetically confirmed CMT. Hereditary motor neuropathy (HMN) accounted for 16.1% (107/666) of HPN, and 43% (46/107) of HPN was genetically confirmed. The most common genes of HMN were HSPB1, aminoacyl tRNA synthetases and SORD mutations, which accounted for 56.5% (26/46) of the patients with genetically confirmed HMN. Most genes associated with HMN could cause different phenotypes. HMN and CMT shared many genes (e.g. HSPB1, GARS, IGHMBP2). Some genes associated with dHMN-plus shared genes associated with amyotrophic lateral sclerosis (KIF5A, FIG4, DCTN1, SETX, VRK1), hereditary spastic paraplegia (KIF5A, ZFYVE26, BSCL2) and spinal muscular atrophy (MORC2, IGHMBP, DNAJB2), suggesting that HMN was a continuum rather than a distinct entity. Hereditary sensor and autosomal neuropathy (HSAN) accounted for a small proportion of 2.6% (17/666) in HPN. The most common pathogenic gene was SPTLC1 mutation. TTR was the main gene causing hereditary amyloid peripheral neuropathy. The most common types of gene mutations were p.A117S and p.V50M. The symptoms were characterized by late-onset and prominent autonomic nerve involvement. CONCLUSION: CMT and HMN are the most common diseases of HPN. There is a large overlap between HMN and motor-CMT2 pathogenic genes, and some HMN pathogenic genes overlap with amyotrophic lateral sclerosis, hereditary spastic hemiplegia and spinal muscular atrophy, suggesting that there may be a potential common pathogenic pathway between different diseases.

Novel variants broaden the phenotypic spectrum of PLEKHG5-associated neuropathies.

BACKGROUND AND PURPOSE: Pathogenic variants in PLEKHG5 have been reported to date to be causative in three unrelated families with autosomal recessive intermediate Charcot-Marie-Tooth disease (CMT) and in one consanguineous family with spinal muscular atrophy (SMA). PLEKHG5 is known to be expressed in the human peripheral nervous system, and previous studies have shown its function in axon terminal autophagy of synaptic vesicles, lending support to its underlying pathogenetic mechanism. Despite this, there is limited knowledge of the clinical and genetic spectrum of disease. METHODS: We leverage the diagnostic utility of exome and genome sequencing and describe novel biallelic variants in PLEKHG5 in 13 individuals from nine unrelated families originating from four different countries. We compare our phenotypic and genotypic findings with a comprehensive review of cases previously described in the literature. RESULTS: We found that patients presented with variable disease severity at different ages of onset (8-25 years). In our cases, weakness usually started proximally, progressing distally, and can be associated with intermediate slow conduction velocities and minor clinical sensory involvement. We report three novel nonsense and four novel missense pathogenic variants associated with these PLEKHG5-associated neuropathies, which are phenotypically spinal muscular atrophy (SMA) or intermediate Charcot-Marie-Tooth disease. CONCLUSIONS: PLEKHG5-associated neuropathies should be considered as an important differential in non-5q SMAs even in the presence of mild sensory impairment and a candidate causative gene for a wide range of hereditary neuropathies. We present this series of cases to further the understanding of the phenotypic and molecular spectrum of PLEKHG5-associated diseases.

Clinical and radiological characterization of novel FIG4-related combined system disease with neuropathy.

Variants in the FIG4 gene, which encodes a phosphatidylinositol-3,5-bisphosphatase lead to obstruction of endocytic trafficking, causing accumulation of enlarged vesicles in murine peripheral neurons and fibroblasts. Bi-allelic pathogenic variants in FIG4 are associated with neurological disorders including Charcot-Marie-Tooth disease type-4J (CMT4J) and Yunis-Varón syndrome (YVS). We present four probands from three unrelated families, all homozygous for a recurrent FIG4 missense variant c.506A>C p.(Tyr169Ser), with a novel phenotype involving features of both CMT4J and YVS. Three presented with infant-onset dystonia and one with hypotonia. All have depressed lower limb reflexes and distal muscle weakness, two have nerve conduction studies (NCS) consistent with severe sensorimotor demyelinating peripheral neuropathy and one had NCS showing patchy intermediate/mildly reduced motor conduction velocities. All have cognitive impairment and three have swallowing difficulties. MRI showed cerebellar atrophy and bilateral T2 hyperintense medullary swellings in all patients. These children represent a novel clinicoradiological phenotype and suggest that phenotypes associated with FIG4 missense variants do not neatly fall into previously described diagnoses but can present with variable features. Analysis of this gene should be considered in patients with central and peripheral neurological signs and medullary radiological changes, providing earlier diagnosis and informing reproductive choices.

Towards a functional pathology of hereditary neuropathies.

A growing number of hereditary neuropathies have been assigned to causative gene defects in recent years. The study of human nerve biopsy samples has contributed substantially to the discovery of many of these neuropathy genes. Genotype-phenotype correlations based on peripheral nerve pathology have provided a comprehensive picture of the consequences of these mutations. Intriguingly, several gene defects lead to distinguishable lesion patterns that can be studied in nerve biopsies. These characteristic features include the loss of certain nerve fiber populations and a large spectrum of distinct structural changes of axons, Schwann cells and other components of peripheral nerves. In several instances the lesion patterns are directly or indirectly linked to the known functions of the mutated gene. The present review is designed to provide an overview on these characteristic patterns. It also considers other aspects important for the manifestation and pathology of hereditary neuropathies including the role of inflammation, effects of chemotherapeutic agents and alterations detectable in skin biopsies.

Molecular Epidemiology of Charcot-Marie-Tooth Disease in Northern Ostrobothnia, Finland: A Population-Based Study.

BACKGROUND: Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuromuscular disorder with a population prevalence of 9.7-82.3/100,000. In this study, we have estimated the prevalence of CMT and its subtypes in Finland and examined the frequency of molecular etiologies. METHODS: A population-based survey included adult patients with peripheral neuropathy from the province of Northern Ostrobothnia, Finland. Secondary causes of peripheral polyneuropathy were excluded and patients with clinical and neurophysiological features pertinent with CMT were included. Molecular diagnostics was carried out when DNA was available. RESULTS: We found 107 subjects with CMT yielding a prevalence 34.6/100,000 in Northern Ostrobothnia. The heterozygous point mutation p.His123Arg in ganglioside induced differentiation associated protein 1 (GDAP1) was found in 31.5% and peripheral myelin protein 22 (PMP22) duplication in 16.9% of the affected. Point mutations in myelin protein zero, mitofusin 2, and gap junction protein beta 1 accounted for 6.7% of the cases. In addition, 18 persons had hereditary neuropathy with liability to pressure palsies and 15 of them carried the PMP22 deletion. CONCLUSIONS: The prevalence of CMT in Northern Ostrobothnia, Finland, seems to be slightly higher than those in previous studies in European populations. Founder mutation in the GDAP1 gene accounts for a large part of the genetically defined CMT2 in Finland.

Relationship between care pathway features and use or non-use of orthotic devices by individuals with Charcot-Marie-Tooth disease: a cross-sectional, exploratory study.

PURPOSE: Orthotic devices may be prescribed for the management of foot and ankle deformities caused by Charcot-Marie-Tooth disease (CMT). However, the actual use of these devices is variable. No studies have evaluated the impact of prescription, delivery and follow-up of orthotic devices on their use.We aimed to describe the relationship between the pathways followed by individuals with CMT and orthotic device use. MATERIALS AND METHODS: Exploratory, cross-sectional, 35-item survey of orthotic device management. Individuals with CMT were recruited from CMT-France Association. RESULTS: Of the 940 respondents, 795 were included, mean age of 52.9 (SD 16.9) years. Rate of orthotic device use was 49.2% (391/795). The most frequent reason for non-use was a poor fit. Non-use was related to the orthotic device type, the health professionals consulted, and the severity of the CMT-related impairments. Follow-up visits (38.7%), re-evaluation of orthotic devices (25.3%) and consultations with the Physical and Rehabilitation Medicine physician were infrequent (28.3%). CONCLUSIONS: Orthotic devices are massively underused. Follow-up and re-evaluation are infrequent. Care pathways, prescription and delivery of orthotic devices must be optimized to meet the expectations of people with CMT. Device fitting, individual needs, and changes in the clinical state must be re-evaluated regularly by specialists to improve orthotic device use.Implications for rehabilitationFoot deformities and foot drop contribute to disability in people with Charcot Marie Tooth Disease but use of orthotic devices is poor.To improve orthotic device use, regular multidisciplinary consultations and regular re-evaluation of the device by specialists in neuro-orthopaedics are important.The device fit should be regularly re-evaluated by the prescribing doctor or the practitioner who made the device.Regular multimodal evaluation of foot deformity, including muscle strength and length, and the individual's needs and expectations is also important to improve orthotic device use.

Effect of Ankle-Foot Orthoses in Pediatric Patients with Hereditary Motor-Sensory Neuropathy: A Case Series Study.

(1) Aims: to evaluate the effect on gait performance and standing stability of ankle-foot orthoses (AFO) in pediatric patients with hereditary motor-sensory neuropathy (HMSN). (2) Methods: a retrospective case-series study including three adolescents (S1, S2, S3, mean age 14 years) with HMSN. The subjects were evaluated barefoot, with carbon AFO (Botter) and with solid AFO (SAFO) by means of: gait analysis, stabilometry and gait functional tests (10 Meter Walk Test, 2 Minute Walk Test). Finally, the CSD-OPUS questionnaire was administered to the assess satisfaction and impact of the orthoses on life quality. (3) Results: orthoses improved gait and stability performance. Botter allowed greater ankle movement than SAFO and provided greater push-off power. This, combined with the carbon elastic energy return, might explain better performances in the 2MWT, with a larger distance traveled compared to SAFO for both S1 (110 m vs. 72 m) and S2 (170 m vs. 155 m) and, compared to barefoot walking, also for S3 (211 m vs. 160 m), for which SAFO analysis was not available. Both orthoses improved performance at the stabilometric analysis. The CSD-OPUS questionnaire showed a significantly higher level of satisfaction with Botter for the subjects (S1, S2) who completed the comparison. (4) Conclusions: Both orthoses improved gait and standing, though Botter proved to be better tolerated and more effective in improving gait endurance.

Vibration perception among children and adolescents with Charcot-Marie-tooth disease and implications for foot posture.

BACKGROUND: Alterations in vibration perception among children and adolescents with Charcot-Marie-Tooth disease might explain observed changes in foot posture. Therefore, this cross-sectional study compared the vibration perception of the lower limbs in youths with and without Charcot-Marie-Tooth disease and verified the cut-off value of the distal vibration perception for the Charcot-Marie-Tooth group. In addition, associations between dynamic plantar pressure, vibration perception and isometric muscle strength were investigated. METHODS: Participants aged 9-18 (Charcot-Marie-Tooth group n = 32; Typical group n = 32) had vibration perception measured by a 128-Hz graduated tuning fork. The static and dynamic foot posture were evaluated by the Foot Posture Index and pressure distribution measuring system, respectively. For the Charcot-Marie-Tooth group, a hand-held dynamometer evaluated the isometric muscle strength of the lower limbs. FINDINGS: Children with Charcot-Marie-Tooth disease presented impaired vibration perception at the distal phalanx of the hallux and head of the first metatarsal compared to their typically developing peers, while adolescents with Charcot-Marie-Tooth disease showed impairment in all the tested regions compared to their typically developing peers. The cut-off value for vibration perception for participants with Charcot-Marie-Tooth disease was 5.7, considering the original grade of the tuning-fork 128 Hz. Among the associations established for the Charcot-Marie-Tooth group, a greater vibration perception at the distal phalanx of the hallux was associated with a longer rearfoot contact time (ß = 31.02, p = 0.04). INTERPRETATION: These new findings may guide the clinical evaluation and rehabilitation treatment for children and adolescents with Charcot-Marie-Tooth disease.

Multiple tendon transfer for a case of radial nerve palsy in hereditary neuropathy with liability to pressure palsy.

Hereditary neuropathy with liability to pressure palsy (HNPP) is a rare autosomal dominant disease characterized by focal, recurrent, demyelinating peripheral neuropathies. It is caused by deletions of the gene encoding for peripheral myelin protein 22 (PMP22) on chromosome 17. While it may range widely, the most common clinical presentation is an acute, focal mononeuropathy with numbness or muscle weakness after trauma or compression. Diagnostic tools include electrophysiological studies, genetic tests and nerve biopsies. There is no standard surgical or pharmacological treatment. The course of the disease is usually benign, with spontaneous improvement after most episodes of peripheral nerve palsy. HNPP is best managed by early detection, preventative measures, and subsequent treatment of symptoms. According to the medical literature, operative treatment was undertaken in few cases and limited to decompression of the nerve at the classic entrapment sites of the carpal or cubital tunnels. We present a case of multiple tendon transfer (pronator teres to extensor carpi radialis brevis and flexor carpi radialis to extensor digitorum communis) with a two-year follow-up in a 24-year-old woman with HNPP who was affected by irreversible radial nerve palsy, and conclude with a review of the medical literature related to the disease.

Neuralgic Amyotrophy with Concomitant Hereditary Neuropathy with Liability to Pressure Palsy as a Cause of Dropped Shoulder in a Child after Human Papillomavirus Vaccination: A Case Report.

Hereditary neuropathy with liability to pressure palsy (HNPP) makes nerves increasingly susceptible to mechanical pressure at entrapment sites. Neuralgic amyotrophy (NA) can cause sudden regional weakness following events to which the patient is immunologically predisposed, such as vaccination. However, NA related to human papilloma virus (HPV) vaccination is seldom reported. We describe the case of a child with NA as the cause of a dropped shoulder following the administration of the HPV vaccine. Underlying asymptomatic HNPP was confirmed in this patient based on the electrodiagnostic findings and genetic analysis. We speculate that HPV vaccination elicited an immune-mediated inflammatory response, resulting in NA. Our patient with pre-existing HNPP might be vulnerable to the occurrence of an immune-mediated NA, which caused the dropped shoulder.

A child resides within a young adult: The first reported case of Alström syndrome in Bangladesh.

A 32-year-old male case with short stature presented to us with audio-visual impairment, obesity, impaired glucose tolerance, dyslipidemia, and hypogonadism. The single-gene genetic analysis revealed an ALMS1 gene mutation. A diagnosis of ALMS was reached for meeting one major and four minor criteria.

Health-related Quality of Life and Satisfaction with German Health Care Services in Patients with Charcot-Marie-Tooth Neuropathy.

BackgroundCharcot-Marie-Tooth (CMT) neuropathies entail a large group of diseases with different gene mutation patterns, which produce heterogeneous phenotypes. Although health-related quality of life (HRQOL) is significantly impaired, a comprehensive assessment of HRQOL in CMT patients in Germany considering phenotypical heterogeneity represented a research gap.ObjectiveThe aim was to assess HRQOL and the satisfaction with health care in CMT patients in Germany.MethodsCMT patients > 15 years with a genetically confirmed CMT subtype were recruited through a national CMT patient registry. HRQOL was assessed using the EQ-5D-5L questionnaire. Furthermore, subjective impairments in daily or work activities and satisfaction with health care were assessed using 4-point scales.ResultsHRQOL in CMT patients (n = 385) was impaired compared to the German population. Most patients reported problems in the dimension mobility (89.6%), pain/discomfort (89.4%) and usual activities (81.0%). Except for patients with hereditary neuropathy with liability to pressure palsy (HNPP), we found no differences in HRQOL between the CMT subtypes. 72.0%of CMT patients were satisfied with available health care services. However, patients reported to expect more CMT-specific knowledge and support as well as easier prescription and cost coverage procedures from health professionals and insurances.ConclusionsThe patient-reported outcomes in the assessed CMT cohort elucidate the need for more specific health care services that also address the heterogeneous phenotypes. Although the assessment has been limited to the German health services setting, insights may be applicable to CMT-specific care in other national settings.

Effectiveness of a specific physical therapy program for Charcot-Marie-Tooth on sleep quality, pain perception, and nocturnal cramps: a pilot study.

Introduction: Chronic pain, nocturnal cramps, and sleep alterations are prevalent symptoms and signals in Charcot-Marie-Tooth disease patients. Sleep and pain are bidirectionally related and physical therapy can improve the binomial sleep and pain/nocturnal cramps. Therefore, we hypothesized that the application of a specific physical therapy program for Charcot-Marie-Tooth disease would improve sleep quality, pain perception, and nocturnal cramps. Material and Methods: A non-randomized controlled study that included 9 Charcot-Marie-Tooth disease patients (intervention group - physical therapy program) and 8 controls (active control group - booklet on sleep hygiene). The intervention lasted 8 weeks, three sessions per week. The effects were evaluated ten days before (baseline) and ten days after the intervention (post). Our primary outcome was sleep quality (subjective and objective, assessed by Pittsburgh sleep quality index and actigraphy, respectively); and secondary outcomes were pain perception (brief pain inventory) and nocturnal cramps (self-report). Results: The program was able to improve the subjective sleep quality (p=0.005) and nocturnal cramps (p<0.001) but had no effect on actigraphy data (p>0.05) neither on pain perception (p>0.05). Conclusion: Our initial hypothesis was partially corroborated: the improvement in subjective quality of sleep and nocturnal cramps is already beneficial for the health promotion of the volunteers in this study affected by the disease. Our findings may serve as a basis for future research to develop a program focused on the treatment of analgesia, which can improve pain perception and alter the objective quality of sleep.

Dynamic plantar pressure patterns in children and adolescents with Charcot-Marie-Tooth disease.

BACKGROUND: The dynamic plantar pressure patterns of children and adolescents with Charcot-Marie-Tooth (CMT) disease and its relationship to musculoskeletal alterations may help to understand the natural history of the disease and improve therapeutic interventions. RESEARCH QUESTION: The study compared dynamic plantar pressure patterns in children and adolescents with and without CMT. It also tested the associations between isometric muscle strength (IMS), passive range of motion (ROM), foot posture and dynamic plantar pressure patterns in CMT. METHODS: This cross-sectional study compared children and adolescents (aged 8-18 years) with CMT (n = 40) with a typical group (n = 40). The plantar pressure distribution during gait was recorded, and the contact area (CA), peak pressure (PP), contact time (CT) and pressure-time integral (PTI) in five foot regions (rearfoot, midfoot lateral, midfoot medial, lateral forefoot and medial forefoot) were analysed. The IMS of the dorsiflexors and plantar flexors, passive ROM, and foot posture were also recorded. RESULTS: PP (medial midfoot and medial forefoot) and PTI (rearfoot, lateral midfoot and medial forefoot) were higher in children with CMT compared with the typical group. The adolescents with CMT presented a less CA (whole foot) and a higher CT (medial midfoot) when compared with typical group. For CMT, in the medial midfoot, plantar flexor IMS associated with PP (ß=-11.54, p = 0.01) and PTI (ß=-3.38, p = 0.04); supinated foot posture associated with PP (ß = 33.89, p = 0.03) and PTI (ß = 12.01, p = 0.03). SIGNIFICANCE: Children with CMT showed clear changes in most of the dynamic plantar pressure variables, while adolescents with CMT showed changes mostly in CA and CT. This information together with the associations established between supinated foot, dorsiflexion ROM and plantar flexions IMS can be useful for guiding rehabilitation professionals in their therapies.

Guided growth in the correction of knee deformity in patients with congenital insensitivity to pain.

BACKGROUND: Orthopedic manifestations of congenital insensitivity to pain (CIP) can be devastating if left untreated. Knee deformities are common in patients with CIP and might lead to joint destruction and loss of walking ability. The purpose of the present study was to report the results and complications of guided growth procedures around the knee in patients with CIP. METHODS: In a retrospective review, all patients with CIP who underwent guided growth procedures around the knee from 2009 to 2017 at a tertiary referral hospital were evaluated. Patients with secondary insensitivity to pain (e.g., syringomyelia), as well as patients with incomplete records, were excluded. Demographic data, clinical findings, correction rate, and complications were recorded. RESULTS: Ten knees in six patients fulfilled the inclusion criteria. The median age was 10 (range, 5-12), with a mean follow-up of 31 months (range, 16-56). Distal femoral tension-band hemiepiphysiodesis was the most common procedure, followed by proximal tibial hemiepiphysiodesis. The mean correction rate was 0.28°/month for femoral deformity. Staples were removed prematurely in one patient due to extrusion. No cases of infection or skin dehiscence were observed. None of the patients needed a reconstructive knee procedure during the study period. CONCLUSIONS: The findings of this study suggest that guided growth procedures might have a role in the correction of knee deformities in patients with CIP. However, the correction rate is lower than that of typically developing children, patients should be closely followed to prevent complications, and stringent patient selection criteria should be followed to ensure success.

Clinical characteristics of hereditary neuropathy with liability to pressure palsy presenting with monoparesis in the emergency department.

Hereditary neuropathy with liability to pressure palsy (HNPP) is a rare neurological genetic disease caused by deletion of the peripheral myelin protein 22 gene and presents in childhood or young adulthood. We report four cases of HNPP with typical and rare presentations, reflecting the broad clinical spectrum of this disease. Two patients presented with mononeuropathies that are frequently observed in HNPP; the remaining two presented with bilateral neuropathy or mononeuropathy anatomically present in the deep layer. This reflects the broad clinical presentation of HNPP, and clinicians should differentiate these conditions in young patients with monoparesis or bilateral paresis. Although HNPP is currently untreatable, early diagnosis in the emergency department can lead to early detection, eventually resulting in less provocation and recurrence which may cause early motor nerve degeneration.

Late onset CMT2A in a Family with an MFN2 Variant: c.2222T>G (p.Leu741Trp).

Mutations in MFN2 cause a range of Charcot-Marie-Tooth disease (CMT) phenotypes with different inheritance patterns and underlying pathogenic mechanisms. Recently, a family with a dominantly inherited CMT harboring c.2222T>G (p.Leu741Trp) mutation in MFN2 has been reported for the first time. Here, we report a second family also with a dominantly inherited CMT harboring the same mutation, thereby confirming the pathogenicity of this mutation. Interestingly, the disease onset of this second family is much later than the previously reported cases.

Charcot-Marie-Tooth disease: from historical landmarks in Brazil to current care perspectives / Doença de Charcot-Marie-Tooth: dos marcos históricos no Brasil até as perspectivas atuais de cuidado

Abstract Hereditary motor and sensory neuropathy, also known as Charcot-Marie-Tooth disease (CMT), traditionally refers to a group of genetic disorders in which neuropathy is the main or sole feature. Its prevalence varies according to different populations studied, with an estimate between 1:2,500 to 1:10,000. Since the identification of PMP22 gene duplication on chromosome 17 by Vance et al., in 1989, more than 100 genes have been related to this group of disorders, and we have seen advances in the care of patients, with identification of associated conditions and better supportive treatments, including clinical and surgical interventions. Also, with discoveries in the field of genetics, including RNA interference and gene editing techniques, new treatment perspectives begin to emerge. In the present work, we report the most import landmarks regarding CMT research in Brazil and provide a comprehensive review on topics such as frequency of different genes associated with CMT in our population, prevalence of pain, impact on pregnancy, respiratory features, and development of new therapies.

Resumo A neuropatia sensitivo-motora hereditária, também conhecida como doença de Charcot-Marie-Tooth (CMT), tradicionalmente se refere a um grupo de doenças genéticas em que a neuropatia é a principal ou única manifestação. Sua prevalência varia de acordo com as diferentes populações estudadas, com estimativa entre 1:2.500 a 1:10.000. Desde a identificação da duplicação do gene PMP22 no cromossomo 17, por Vance et al., em 1989, mais de 100 genes foram relacionados a esse grupo de doenças e temos visto avanços no atendimento aos pacientes, com identificação de condições associadas e melhores tratamentos de suporte, incluindo intervenções clínicas e cirúrgicas. Além disso, com as descobertas no campo da genética, incluindo técnicas de interferência de RNA e de edição genética, novas perspectivas de tratamento começaram a surgir. No presente trabalho, relatamos os marcos mais importantes sobre a pesquisa de CMT no Brasil e fornecemos uma revisão abrangente sobre tópicos como frequência de diferentes genes associados à CMT em nossa população, prevalência de dor, impacto na gravidez, alterações respiratórias e desenvolvimento de novas terapias.

Accumulating Evidence for Axonal Translation in Neuronal Homeostasis.

The specialized structure of the neuron requires that homeostasis is sustained over the meter or more that may separate a cell body from its axonal terminus. Given this impressive distance and an axonal volume that is many times that of the cell body, how is such a compartment grown during development, re-grown after injury, and maintained throughout adulthood? While early answers to these questions focused on the local environment or the cell soma as supplying the needs of the axon, it is now well-established that the axon has some unique needs that can only be met from within. Decades of research have revealed local translation as an indispensable mechanism of axonal homeostasis during development and regeneration in both invertebrates and vertebrates. In contrast, the extent to which the adult, mammalian axonal proteome is maintained through local translation remains unclear and controversial. This mini-review aims to highlight important experiments that have helped to shape the field of axonal translation, to discuss conceptual arguments and recent evidence that supports local translation as important to the maintenance of adult axons, and to suggest experimental approaches that have the potential to further illuminate the role of axonal translation in neuronal homeostasis.