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.
Neurology. 2021 Jan 19;96(3):e423-e432. doi: 10.1212/WNL.0000000000011054. Epub 2020 Oct 16.
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.
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.
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 (-4, -2, -2, -1). A novel pathogenic variant in the 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.
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.
描述儿科远端遗传性运动神经病（dHMN）的临床、遗传和残疾特征，并确定一种针对小儿遗传性运动感觉神经病（CMT）的经过验证的疗效评估方法，在评估该队列的残疾程度中的效用。
我们回顾了在澳大利亚和西班牙的 2 个三级神经肌肉诊所，对 22 名年龄在 20 岁以下的 dHMN 患者的临床、神经生理和残疾数据进行了评估。在部分患者中，每年使用小儿遗传性运动感觉神经病量表（CMTPedS）评估残疾情况。
共纳入了 19 个家族的 22 名儿童（13 名女性）。14 名患者在生命的第一年就出现了症状。6 名患者存在智力障碍，8 名患者出现了上运动神经元体征。9 个家族中发现了致病性变异，其中更常见于（-4，-2，-2，-1）。在 基因中发现了一种新的致病性变异，并对其进行了表型特征分析。CMTPedS 的残疾程度为中度（平均[标准差]为 18.2[6.3]，n=16），受影响最严重的是平衡和跳远，而感觉项目和握力受影响最小。在 1 年的时间里，CMTPedS 总评分恶化，平均为 1.5 分（标准差为 3.7）或 9%（n=12），但队列内的进展速度存在显著差异。
儿科 dHMN 的遗传特征与成人队列中的遗传特征不同。本研究确定了 CMTPedS 在患有 dHMN 的儿童和青少年中的独特功能限制。
