Herminia Argente-Escrig1, Joshua Burns1, Gabrielle Donlevy1, Marina Frasquet1, Kayla Cornett1, Teresa Sevilla1, Manoj P Menezes2. 1. From the T.Y. Nelson Department of Neurology and Neurosurgery (M.P.M.), The Children's Hospital at Westmead, NSW; University of Sydney School of Health Sciences & Children's Hospital at Westmead (J.B., G.D., K.C., M.P.M.), Sydney, Australia; Health Research Institute Hospital La Fe (H.A.-E., M.F.) and Department of Neurology (H.A.-E, M.F., T.S.), Hospital Universitari i Politècnic La Fe, Valencia, Spain; Centre for Biomedical Network Research on Rare Diseases-CIBERER (H.A.E., T.S.); and Department of Medicine (T.S.), University of Valencia, Spain. 2. From the T.Y. Nelson Department of Neurology and Neurosurgery (M.P.M.), The Children's Hospital at Westmead, NSW; University of Sydney School of Health Sciences & Children's Hospital at Westmead (J.B., G.D., K.C., M.P.M.), Sydney, Australia; Health Research Institute Hospital La Fe (H.A.-E., M.F.) and Department of Neurology (H.A.-E, M.F., T.S.), Hospital Universitari i Politècnic La Fe, Valencia, Spain; Centre for Biomedical Network Research on Rare Diseases-CIBERER (H.A.E., T.S.); and Department of Medicine (T.S.), University of Valencia, Spain. manoj.menezes@health.nsw.gov.au.
Abstract
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. Disability was assessed annually with the CMT Pediatric Scale (CMTPedS) in a subset of individuals. RESULTS: Twenty-two children (13 female) from 19 families were included. Fourteen individuals were symptomatic in the first year of life. Intellectual disability was present in 6 individuals; upper motor neuron signs were seen in 8. Pathogenic variants were found in 9 families, more frequently in BICD2 (BICD2-4, DYNC1H1-2, MFN2-2, GARS-1). A novel pathogenic variant in the GARS gene was detected and characterized phenotypically. Disability was moderate on the CMTPedS (mean [SD] 18.2 [6.3], n = 16), with balance and long jump being the most affected and sensation items and grip strength the least affected. Over 1 year, the CMTPedS total score deteriorated, on average 1.5 points (SD 3.7) or 9% (n = 12), with significant variability in the rate of progression within the cohort. CONCLUSIONS: The genetic profile of pediatric dHMN is different from that identified in adult cohorts. This study has identified distinct functional limitations for the CMTPedS in children and adolescents with dHMN.
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. Disability was assessed annually with the CMT Pediatric Scale (CMTPedS) in a subset of individuals. RESULTS: Twenty-two children (13 female) from 19 families were included. Fourteen individuals were symptomatic in the first year of life. Intellectual disability was present in 6 individuals; upper motor neuron signs were seen in 8. Pathogenic variants were found in 9 families, more frequently in BICD2 (BICD2-4, DYNC1H1-2, MFN2-2, GARS-1). A novel pathogenic variant in the GARS gene was detected and characterized phenotypically. Disability was moderate on the CMTPedS (mean [SD] 18.2 [6.3], n = 16), with balance and long jump being the most affected and sensation items and grip strength the least affected. Over 1 year, the CMTPedS total score deteriorated, on average 1.5 points (SD 3.7) or 9% (n = 12), with significant variability in the rate of progression within the cohort. CONCLUSIONS: The genetic profile of pediatric dHMN is different from that identified in adult cohorts. This study has identified distinct functional limitations for the CMTPedS in children and adolescents with dHMN.
Authors: Amila Zuko; Moushami Mallik; Robin Thompson; Emily L Spaulding; Anne R Wienand; Marije Been; Abigail L D Tadenev; Nick van Bakel; Céline Sijlmans; Leonardo A Santos; Julia Bussmann; Marica Catinozzi; Sarada Das; Divita Kulshrestha; Robert W Burgess; Zoya Ignatova; Erik Storkebaum Journal: Science Date: 2021-09-01 Impact factor: 63.714