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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.
Glossary
- CHW=
- The Children's Hospital at Westmead;
- CMAP=
- compound motor unit action potentials;
- CMT=
- Charcot-Marie-Tooth disease;
- CMTPedS=
- CMT Pediatric Scale;
- dHMN=
- distal hereditary motor neuropathies;
- HDAC=
- histone deacetylase;
- HLF=
- Hospital Universitari i Politècnic La Fe;
- NCS=
- nerve conduction studies;
- SMA-LED=
- spinal muscular atrophy, lower extremity dominant;
- UMN=
- upper motor neuron
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received May 31, 2020.
- Accepted in final form September 1, 2020.
- © 2020 American Academy of Neurology
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