PDF(Pubmed)
Abstract：
SCN4A mutations have been shown to be associated with myotonia, paramyotonia congenita, and periodic paralyses. More recently, loss-of-function variants in the SCN4A gene were also noted to be associated with rarer, autosomal recessive forms of congenital myasthenic syndrome and congenital myopathy. Diagnosis is challenging as the initial clinical presentation and histological features on muscle biopsies are non-specific. We report a Han Chinese patient presented with congenital myopathy with two missense SCN4A variants. The patient had an antenatal history of reduced fetal movements, polyhydramnios and a very preterm birth. At birth, she was noted to have low Apgar score, respiratory distress syndrome and hypotonia. Delayed motor development was noted in early childhood. Dysmorphic features such as an elongated face, dolichocephaly and high arched palate were present. At 16 years of age, the patient developed progressive muscle weakness and was wheelchair-bound by age 20. Muscle biopsy revealed non-specific changes only. Targeted hereditary myopathy panel testing by next generation sequencing revealed two previously unreported missense variants c.1841A > T p.(Asn614Ile) and c.4420G > A p.(Ala1474Thr) in the SCN4A gene. The clinical features of SCN4A-related congenital myopathy and myasthenic syndrome were reviewed. This case exemplifies the utility of next generation sequencing in the diagnosis of undifferentiated muscle disease.
摘要：
SCN4A突变已被证明与肌强直有关，先天性副肌强直,和周期性瘫痪。最近,SCN4A基因中的功能缺失变异也被注意到与稀有有关，先天性肌无力综合征和先天性肌病的常染色体隐性形式。由于肌肉活检的初始临床表现和组织学特征是非特异性的，因此诊断具有挑战性。我们报告了一名患有先天性肌病的汉族患者，患有两种错义SCN4A变异。该患者有胎动减少的产前病史，羊水过多和早产。出生时,她的阿普加分数很低,呼吸窘迫综合征和张力减退。在儿童早期注意到运动发育延迟。畸形特征，如拉长的脸，存在头颅畸形和高拱形腭。16岁时,患者出现进行性肌无力,在20岁时开始坐轮椅.肌肉活检仅显示非特异性变化。通过下一代测序进行的靶向遗传性肌病小组测试显示，SCN4A基因中有两个以前未报告的错义变体c.1841A>Tp。（Asn614Ile）和c.4420G>Ap。（Ala1474Thr）。本文对SCN4A相关先天性肌病和肌无力综合征的临床特点进行了综述。这种情况举例说明了下一代测序在未分化肌肉疾病诊断中的实用性。
