新生儿线状体肌病伴NEB变异及良好3年结局：一例病例报告

文献信息

中文摘要

理由： 线状体肌病（NM）是一种罕见的先天性肌病，以肌无力和肌张力低下为特征。严重的 neonatal 疾病可能涉及呼吸衰竭和延髓功能障碍。nebulin基因（NEB）变异是常见的遗传病因，但基因型-表型关系和预后仍存在差异。
患者关注： 一名女性新生儿在出生后不久出现发绀、心动过缓、呼吸窘迫和肌张力低下。她需要有创机械通气，随后反复出现呼吸功能恶化、难以脱离呼吸机支持、喂养差、呕吐和呛咳、吸吮和吞咽无力以及原始反射减弱。
诊断： 临床表型和三人全外显子组测序结果支持与NEB变异相关的NM临床诊断。测序发现一个母源遗传的致病性移码变异c.23910_23911delAG（p.Arg7970SerfsTer9），以及2个被归类为意义不确定变异的错义变异：母源遗传的c.5615C>T（p.Pro1872Leu）和父源遗传的c.19550G>A（p.Arg6517His）。肌肉活检、等位基因定相和功能研究未能进行；因此，分子诊断并不确定。
干预： 患者接受了有创和无创呼吸支持、氧疗、喂养和对症管理、系列神经系统评估以及神经康复。
结果： 新生儿行为神经学评估评分从第7天的25分升至第14天的30分和第28天的36分。呼吸功能、喂养和肌张力逐渐改善，得以撤除呼吸支持。出院后每6个月进行的丹佛发育筛查测验评估未报告发育异常。3岁时，未观察到明显的肌张力低下、运动障碍或其他临床可见的运动损害。
经验教训： 与NEB变异相关的新生儿NM可能表现为危及生命的呼吸和延髓功能障碍，但随后可出现良好的早期发育过程。三人全外显子组测序可能有助于病因评估，但在缺乏组织病理学、定相和功能证据时，NEB变异需要谨慎解读。严重的新生儿表现不应被视为必然提示预后不良，仍需继续进行神经肌肉、呼吸、喂养、骨科和发育监测。

英文摘要

RATIONALE: Nemaline myopathy (NM) is a rare congenital myopathy characterized by muscle weakness and hypotonia. Severe neonatal disease may involve respiratory failure and bulbar dysfunction. Variants in the nebulin gene (NEB) are a common genetic cause, but genotype-phenotype relationships and prognosis remain variable.
PATIENT CONCERNS: A female neonate developed cyanosis, bradycardia, respiratory distress, and hypotonia shortly after birth. She required invasive mechanical ventilation and later experienced recurrent respiratory deterioration, difficulty weaning from ventilatory support, poor feeding, vomiting and choking, weak sucking and swallowing, and diminished primitive reflexes.
DIAGNOSES: The clinical phenotype and trio whole-exome sequencing findings supported a clinical diagnosis of NM associated with NEB variants. Sequencing identified a maternally inherited pathogenic frameshift variant, c.23910_23911delAG (p.Arg7970SerfsTer9), and 2 missense variants classified as variants of uncertain significance: maternally inherited c.5615C>T (p.Pro1872Leu) and paternally inherited c.19550G>A (p.Arg6517His). Muscle biopsy, allelic phasing, and functional studies were unavailable; therefore, the molecular diagnosis was not definitive.
INTERVENTIONS: The patient received invasive and noninvasive respiratory support, oxygen therapy, feeding and symptomatic management, serial neurological assessments, and neurological rehabilitation.
OUTCOMES: The Neonatal Behavioral Neurological Assessment score increased from 25 on day 7 to 30 on day 14 and 36 on day 28. Respiratory function, feeding, and muscle tone gradually improved, allowing respiratory support to be withdrawn. Denver Developmental Screening Test assessments performed at 6-month intervals after discharge identified no reported developmental abnormalities. At 3 years of age, no apparent hypotonia, movement disorder, or other clinically evident motor impairment was observed.
LESSONS: Neonatal NM associated with NEB variants may present with life-threatening respiratory and bulbar dysfunction yet be followed by a favorable early developmental course. Trio whole-exome sequencing may facilitate etiological evaluation, but NEB variants require cautious interpretation when histopathological, phasing, and functional evidence is unavailable. A severe neonatal presentation should not be regarded as indicating an invariably poor prognosis, and continued neuromuscular, respiratory, feeding, orthopedic, and developmental surveillance remains warranted.