Clinical, Genetic, and Disability Profile of Pediatric Distal Hereditary Motor Neuropathy
Herminia Argente-Escrig1, Joshua Burns1, Gabrielle Donlevy1
1From 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.
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.
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