背景:肌源性关节炎多重同源3型(AMC-3),是一种罕见的先天性疾病,其特征是严重的张力减退,球杆脚,和多个关节挛缩通常影响手臂和腿在出生前开始。
方法:我们报告了一名出生在第四代近亲家庭一级表亲的足月新生儿,有胎儿运动减少的产前病史。出生时,他被发现有双足,关节病,严重的低张力,和缺乏深肌腱反射。患者出现呼吸困难,可能归因于他的全身性严重张力减退,需要机械通风。他的肌酐磷酸激酶,肌电图,脑磁共振成像正常。该病例的基因诊断需要全外显子组测序(WES)。WES在突触核包膜蛋白1[SYNE1]基因中鉴定了一种新的纯合变体c.23415-3799C>Gp。20个生物信息学计算机程序中有7个预测了该变体的致病作用。父母和兄弟姐妹中变异的分离分析表明,父母和一个兄弟姐妹都是同一突变的杂合,这证明了变异的重要性及其常染色体隐性遗传方式。
结论:AMC3应该怀疑胎儿运动减少的患者,严重的低张力,深肌腱反射缺失,和关节病。SYNE1基因突变可能是潜在的遗传缺陷,分子遗传检测可以证明诊断。
BACKGROUND: Myogenic Arthrogryposis Multiplex Congenita type 3 (AMC-3), is a rare congenital condition characterized by severe hypotonia, club feet, and multiple joint contractures often affecting both arms and legs which start prior to birth.
METHODS: We report a full-term neonate born to first-degree cousins from fourth-generation consanguineous families, who had with antenatal history of reduced fetal movements. At birth, he was noticed to have bilateral club feet, arthrogryposis, severe hypotonia, and absent deep tendon reflexes. The patient developed difficulty in breathing probably attributed to his generalized severe hypotonia, necessitating mechanical ventilation. His creatinine-phospho-kinase, electromyogram, and brain magnetic resonance imaging were normal. Whole-exome sequencing (WES) was requested for the genetic diagnosis of the
case. WES identified a novel homozygous variant c.23415-3799C > G p. in the synaptic nuclear envelope protein1 [SYNE1] gene. Seven out of 20 bioinformatic in silico programs predicted a pathogenic effect for this variant. Segregation analysis of the variant in the parents and siblings revealed that both parents and one sibling were heterozygous for the same mutation which proved the variant significance and its autosomal recessive pattern of inheritance.
CONCLUSIONS: AMC3 should be suspected in patients with decreased fetal movements, severe hypotonia, absent deep tendon reflexes, and arthrogryposis. SYNE1 gene mutations can be the underlying genetic defect and molecular genetic testing can prove the diagnosis.