Joshua Burns pediatric CMT

BACKGROUND AND AIMS: Riboflavin transporter deficiency (RTD) is a progressive inherited neuropathy of childhood onset, characterised clinically by pontobulbar palsy, sensory ataxia, sensorineural deafness, muscle weakness, optic atrophy and respiratory failure. A robust and responsive functional outcome measure is essential for future clinical trials of disease-modifying therapies including genetic therapies. The Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS) is a well-validated outcome measure for CMT and related neuropathies, and might have utility for measuring disease progression in individuals with RTD...

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the impact of body mass index (BMI) on disease progression over 2 years in children with Charcot-Marie-Tooth disease (CMT). METHODS: BMI was classified in 242 participants aged 3-20 years with CMT enrolled in the Inherited Neuropathy Consortium, using the International Obesity Task Force (based on adult BMI values, kg/m2 ) criteria. Groups were categorized as severely underweight (BMI <17 kg/m2 ), underweight (BMI ≥17 to <18...

OBJECTIVE: To evaluate the parent-proxy version of the pediatric Charcot Marie Tooth specific quality of life (pCMT-QOL) outcome instrument for children aged 7 or younger with CMT. We have previously developed and validated the direct-report pCMT-QOL for children aged 8-18 years and a parent proxy version of the instrument for children 8-18 years old. There is currently no CMT-QOL outcome measure for children aged 0-7 years old. METHODS: Testing was conducted in parents or caregivers of children aged 0-7 years old with CMT evaluated at participating INC sites from the USA, United Kingdom, and Australia...

Charcot-Marie-Tooth disease (CMT) reduces health-related quality of life (QOL) in children. We have previously developed and validated the English and Italian versions of the pediatric CMT-specific QOL outcome measure (pCMT-QOL) for children aged 8 to 18. There is currently no parent-proxy CMT QOL outcome measure for use in clinical trials, which could provide complementary information in these children and adolescents. This study describes the validation studies conducted to develop the parent-proxy version of the pCMT-QOL outcome measure for children aged 8 to 18 years old...

BACKGROUND AND OBJECTIVES: This study examined the association between body mass index (BMI) and disability in children with Charcot-Marie-Tooth disease (CMT). METHODS: We conducted a cross-sectional analysis of 477 patients with CMT who were 3 to 20 years of age from the Inherited Neuropathy Consortium and 316 age- and sex-matched healthy children from the 1,000 Norms Project. BMI was categorized according to the International Obesity Task Force (IOTF) criteria, and BMI categorization was compared with healthy children...

Mitofusin-2 (MFN2) is one of two ubiquitously expressed homologous proteins in eukaryote cells, playing a critical role in mitochondrial fusion. Mutations in MFN2 (most commonly autosomal dominant) cause Charcot-Marie-Tooth disease type 2A (CMT2A), the commonest axonal form of CMT, with significant allelic heterogeneity. Previous, moderately-sized, cross sectional genotype-phenotype studies of CMT2A have described the phenotypic spectrum of the disease, but longitudinal natural history studies are lacking. In this large multicentre prospective cohort study of 196 patients with dominant and autosomal recessive CMT2A, we present an in-depth genotype-phenotype study of the baseline characteristics of patients with CMT2A and longitudinal data (1-2 years) to describe the natural history...

OBJECTIVE: Charcot-Marie-Tooth disease (CMT) reduces health-related quality of life (QOL), especially in children. Defining QOL in pediatric CMT can help physicians monitor disease burden clinically and in trials. We identified items pertaining to QOL in children with CMT and conducted validation studies to develop a pediatric CMT-specific QOL outcome measure (pCMT-QOL). METHODS: Development and validation of the pCMT-QOL patient-reported outcome measure were iterative, involving identifying relevant domains, item pool generation, prospective pilot testing and clinical assessments, structured focus-group interviews, and psychometric testing...

OBJECTIVE: To describe the clinical, genetic, and disability profile of pediatric distal hereditary motor neuropathy (dHMN) and to determine the utility of an outcome measure validated for children with Charcot-Marie-Tooth disease (CMT) in assessing disability in this cohort. METHODS: We reviewed the clinical, neurophysiologic, and disability data on individuals with dHMN, evaluated before the age of 20 years, at 2 tertiary neuromuscular clinics in Australia and Spain...

BACKGROUND: The Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS) has been used to measure aspects of disability in children with all types of Charcot-Marie-Tooth disease (CMT). OBJECTIVE: To translate and cross-culturally adapt the CMTPedS into Brazilian-Portuguese and determine its reliability and validity. METHODS: The translation and cross-cultural adaptation followed international guidelines recommendations. Twenty individuals with CMT were assessed...

The CMT Pediatric Scale (CMTPedS) is a reliable, valid, and responsive clinical outcome measure of disability in children with CMT. The aim of this study was to identify the most responsive patient subset(s), based on the standardized response mean (SRM), to optimize the CMTPedS as a primary outcome measure for upcoming clinical trials. Analysis was based on a 2-year natural history data from 187 children aged 3-20 years with a range of CMT genetic subtypes. Subsets based on age (3-8 years), disability level (CMTPedS score 0-14), and CMT type (CMT1A) increased the SRM of the CMTPedS considerably...

BACKGROUND: Disability related to the progressive and degenerative neuropathies known collectively as Charcot-Marie-Tooth disease (CMT) affects gait and function, increasing with age and influencing physical activity in adults with CMT. The relationship between CMT-related disability, ambulatory function and physical activity in children and adolescents with CMT is unknown. METHOD: A cross-sectional case-controlled study of physical activity in 50 children with CMT and age- and gender-matched typically developing (TD) controls [mean age 12...

Charcot-Marie-Tooth disease (CMT) causes disabling cavovarus foot deformity. Orthopaedic surgery is performed in severe cases; however few studies have investigated whether surgery improves health outcomes during childhood. This study investigated the impact of cavovarus surgery on validated physical, functional, parent/self-reported and biomechanical measures in 21 consecutive patients (mean age at surgery 12.5 years, SD 2.7) evaluated before and after surgery (mean duration 15.7 months, SD 5.9), and compared to natural history data from 206 children with CMT...

INTRODUCTION: Balance impairment contributes to gait dysfunction, falls, and reduced quality of life in adults with Charcot-Marie-Tooth disease (CMT) but has been minimally examined in pediatric CMT. METHODS: The CMT Pediatric Scale (CMTPedS) was administered to 520 children with CMT. Associations between balance function (Bruininks-Oseretsky Test of Motor Proficiency [BOT-2]) and sensorimotor and gait impairments were investigated. RESULTS: Daily trips/falls were reported by 42...

Many genetic subtypes of Charcot-Marie-Tooth disease (CMT) show signs of symptomatic disease during the earliest years of life. This might be the ideal time to intervene before progression of clinical sequelae due to demyelination and axonal loss. In the absence of disease-specific clinical trial outcome measures for CMT during infancy and early childhood the aim of this study was to develop and validate a functional measure of disease severity, known as the Charcot-Marie-Tooth disease Infant Scale (CMTInfS)...

INTRODUCTION: Biomarkers of disease severity in Charcot-Marie-Tooth disease (CMT) are required to evaluate early responses to treatment. In this study we used magnetic resonance imaging (MRI) to evaluate the relationship between muscle volume and intramuscular fat accumulation with weakness, disability, and impaired gait in affected children and adolescents. METHODS: Fifty-five participants underwent MRI of the anterior compartment of the lower leg. Muscle and fat volumes were calculated...

OBJECTIVE: To describe in detail the clinical profile of Charcot-Marie-Tooth disease subtype 3 (CMTX3) to aid appropriate genetic testing and rehabilitative therapy. METHODS: We reviewed the clinical and neurophysiologic profile and CMT Pediatric Scale (CMTPedS) assessments of 11 children with CMTX3. RESULTS: Compared with the more common forms of CMT, CMT1A and CMTX, CMTX3 was characterized by early onset with early and progressive hand weakness...

Résumé Cet article présente le processus de traduction en français du Charcot-Marie-Tooth Disease Pediatric Scale (CMTPedS), le seul outil de mesure validé évaluant la sévérité de la maladie chez les enfants atteints de CMT. Le processus de traduction utilisé s'inspire des lignes directrices de la Food and Drug Administration (FDA). La version préliminaire francophone du CMTPedS a été testée auprès de 14 enfants atteints. Les résultats de l'application démontrent que la passation a été bien tolérée par les enfants et s'est avérée conviviale pour les cliniciens...

OBJECTIVE: To determine the rate of disease progression in a longitudinal natural history study of children with Charcot-Marie-Tooth (CMT) disease. METHODS: Two hundred six (103 female) participants aged 3 to 20 years enrolled in the Inherited Neuropathies Consortium were assessed at baseline and 2 years. Demographic, anthropometric, and diagnostic information were collected. Disease progression was assessed with the CMT Pediatric Scale (CMTPedS), a reliable Rasch-built linearly weighted disability scale evaluating fine and gross motor function, strength, sensation, and balance...

Gait abnormalities reported in childhood Charcot-Marie-Tooth disease (CMT) include foot-drop, reduced ankle power at push-off and increased knee and hip flexion for swing clearance ('steppage-gait'). The purpose of this study was to describe the gait patterns of 60 children aged 6-17 years with CMT (CMTall ) and distinguish differences based on functional weakness using the CMT Pediatric Scale (CMTPedS). Data were captured using Vicon Nexus system and compared to 50 healthy norms. Data were subdivided into three groups denoting increasing severity of dorsiflexion and plantarflexion weakness from the CMTPedS: no difficulty heel or toe walking (CMTND ), difficulty heel walking (CMTDH ), difficulty toe and heel walking (CMTDTH )...

IMPORTANCE: Disease severity of childhood Charcot-Marie-Tooth disease (CMT) has not been extensively characterized, either within or between types of CMT to date. OBJECTIVE: To assess the variability of disease severity in a large cohort of children and adolescents with CMT. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was conducted among 520 children and adolescents aged 3 to 20 years at 8 universities and hospitals involved in the Inherited Neuropathies Consortium between August 6, 2009, and July 31, 2014, in Australia, Italy, the United Kingdom, and the United States...