Jephson Chris G, Mills Nikki A, Pitt Matthew C, Beeson David, Aloysius Annie, Muntoni Francesco, Robb Stephanie A, Bailey C Martin
Department of Otolaryngology, Great Ormond Street Hospital for Children and Institute of Child Health, Great Ormond Street, London, WC1N 3JH, UK.
Int J Pediatr Otorhinolaryngol. 2010 Sep;74(9):991-4. doi: 10.1016/j.ijporl.2010.05.022. Epub 2010 Jun 15.
The congenital myasthenic syndromes (CMS) are a group of genetic disorders of neuromuscular transmission causing fatigable weakness. Symptoms may be present from birth, but diagnosis is often delayed for several years, notably in post-synaptic CMS due to mutations in the DOK7 gene. Recently, we noted a subgroup of children with CMS in whom congenital stridor and bilateral vocal cord palsy predated other symptoms. All had mutations in the DOK7 gene. The purpose of this study was to review our population of DOK7 CMS patients with congenital stridor and assess whether there were other phenotypic features which might raise suspicion of a diagnosis of CMS in the neonatal period, in the absence of limb weakness and ptosis and prompt earlier referral for neurophysiological investigation, genetic diagnosis and appropriate treatment.
A retrospective case review of 11 DOK7 CMS patients at a tertiary referral centre.
Six patients were identified with DOK7 mutations and congenital stridor, four requiring intubation soon after birth. Four patients had a diagnosis of bilateral vocal cord palsy and three required tracheostomy, successfully decannulated in one after 3 years. All six patients had difficulty with feeding, with weak suck and swallow necessitating nasogastric feeding in five, two of whom required gastrostomy. Despite all six children having had neonatal symptoms, the mean age at CMS diagnosis was 5 years and 9 months.
CMS, particularly caused by mutations in the DOK7 gene, is a rare but treatable cause of congenital stridor in the neonate. A combination of congenital stridor, especially with an apparently idiopathic bilateral vocal cord palsy and weak suck and swallow should alert the clinician to the possibility of CMS and prompt early referral for neurophysiology and genetic investigations. Confirmation of a CMS diagnosis enables treatment to be initiated, informed management of the VCP and anticipation of myasthenic symptoms, particularly life-threatening respiratory decompensation. Treatment may allow early decannulation or possible avoidance of tracheostomy. At least 12 genes are known to cause CMS; the presence of congenital stridor may help target genetic diagnosis.
先天性肌无力综合征（CMS）是一组神经肌肉传递的遗传性疾病，可导致易疲劳性肌无力。症状可能自出生时就存在，但诊断往往会延迟数年，尤其是在因DOK7基因突变导致的突触后CMS中。最近，我们注意到一组患有CMS的儿童，其先天性喘鸣和双侧声带麻痹先于其他症状出现。所有患儿均有DOK7基因突变。本研究的目的是回顾我们收治的患有先天性喘鸣的DOK7 CMS患者群体，评估在无肢体无力和上睑下垂的情况下，是否存在其他可能在新生儿期引起对CMS诊断怀疑的表型特征，从而促使更早转诊进行神经生理学检查、基因诊断和适当治疗。
对一家三级转诊中心的11例DOK7 CMS患者进行回顾性病例分析。
6例患者被确定存在DOK7基因突变并伴有先天性喘鸣，其中4例在出生后不久即需要插管。4例患者被诊断为双侧声带麻痹，3例需要气管切开术，其中1例在3年后成功拔管。所有6例患者均存在喂养困难，吸吮和吞咽无力，5例需要鼻饲，其中2例需要胃造瘘术。尽管所有6例患儿在新生儿期均有症状，但CMS诊断的平均年龄为5岁9个月。
CMS，尤其是由DOK7基因突变引起的，是新生儿先天性喘鸣的一种罕见但可治疗的病因。先天性喘鸣，特别是伴有明显特发性双侧声带麻痹以及吸吮和吞咽无力，应提醒临床医生注意CMS的可能性，并促使其尽早转诊进行神经生理学和基因检查。CMS诊断的确认能够启动治疗，对声带麻痹进行明智的管理，并预测肌无力症状，尤其是危及生命的呼吸代偿失调。治疗可能允许早期拔管或避免气管切开术。已知至少有12个基因可导致CMS；先天性喘鸣的存在可能有助于进行基因诊断。
