新生儿神经肌肉疾病25例病例系列报告

25 cases of neonatal neuromuscular disease:A case series report

目的通过分析新生儿期神经肌肉疾病(NMDs)的构成,探讨其临床表现和实验室检查特点,为其诊治提供参考。方法回顾性分析2016年1月1日至2018年12月31日复旦大学附属儿科医院新生儿科收治的确诊NMDs的连续病例资料,包括临床表现、常规实验室检查、肌肉活检(MB)病理、二代基因测序(NGS)及预后结局等。结果 25例NMDs进入本文分析。男14例,女11例。早产9例,足月16例。孕周27+4~41+5(中位数38+3)周,出生体重980~4 050(中位数3 000) g。死亡15例(60%),存活8例(32%),失访2例(8%)。MB时纠正胎龄32+1~51+4(中位数41+3)周。NMDs新生儿期最常见的临床表现为肌张力低下24例(96%),生后需鼻饲喂养(20/22例,90.9%),呼吸支持22例(88%)。64%为神经肌肉相关疾病。NGS检测阳性率92%,其中56%为神经肌肉疾病相关基因。MB病理阳性率76%,其中52.6%为先天性肌病。15例死亡新生儿中,NGS检测阳性率86.7%,其中53.3%为神经肌肉疾病相关基因;MB病理阳性率73.3%,其中40%为先天性肌病。结论新生儿期NMDs起病隐匿,临床表现差异较大,缺乏特异性。详细的病史询问、体格检查、MB病理联合NGS能提高NMDs确诊率,为NMDs的早期诊断和明确治疗提供依据。

Objective To study the spectrum of neonatal neuromuscular diseases(NMDs),to explore the clinical and laboratory characteristics,and to provide a basis for the diagnosis of NMDs.Methods The clinical data of children with confirmed NMDs admitted to the Department of Neonatology,Children's Hospital of Fudan University from January 1,2016 to December 31,2018 were retrospectively analyzed,including clinical presentations,routine laboratory examinations,muscle biopsy(MB),next⁃generation sequencing(NGS)and prognostic outcome,etc.Results A total of 25 cases were enrolled in the study.There were 14 males and 11 females.Nine cases were premature and 16 cases were full term infants.The gestational age was 27+4 to 41+5 weeks(median:38+3 weeks),and the birth weight was 980 to 4,050 g(median:3,000 g).Fifteen cases(60%)died,8 cases(32%)survived,and 2 cases(8%)were lost to follow⁃up.The postmenstrual age of MB was 32+1 to 51+4 weeks(median:41+3 weeks).The most common clinical presentations in the neonatal period were hypotonia 24 cases(96%),requiring nasogastric feeding(20/22 cases,90.9%)and respiratory support 22 cases(88%)after birth.Most of them were neuromuscular⁃related diseases(64%).NGS was positive in 23 cases(92%)with 56%of neuromuscular disease⁃related genes.MB was positive in 19 cases(76%)with 52.6%of congenital myopathy.Among 15 cases of death,86.7%was positive for NGS with 53.3%of neuromuscular disease related genes and 73.3%was positive for MB cases with 40%of congenital myopathy.Conclusion The onset of NMDs in neonatal period was not obvious and the clinical manifestations were quite different and lack of specificity.Detailed medical history,physical examination,MB pathology combined with NGS could improve the diagnosis of NMDs,and provide a basis for the early diagnosis and treatment of NMDs.