Abbott Megan, Jain Mahim, Pferdehirt Rachel, Chen Yuqing, Tran Alyssa, Duz Mehmet B, Seven Mehmet, Gibbs Richard A, Muzny Donna, Lee Brendan, Marom Ronit, Burrage Lindsay C
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.
Department of Medical Genetics, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
Am J Med Genet A. 2017 Oct;173(10):2789-2794. doi: 10.1002/ajmg.a.38383. Epub 2017 Aug 16.
Nemaline myopathy is a rare inherited disorder characterized by weakness, hypotonia, and depressed deep tendon reflexes. It is clinically and genetically heterogeneous, with the most severe phenotype presenting as perinatal akinesia, severe muscle weakness, feeding difficulties and respiratory failure, leading to early mortality. Pathogenic variants in 12 genes, encoding components of the sarcomere or factors related to myogenesis, have been reported in patients affected with the disorder. Here, we describe an early, lethal presentation of decreased fetal movements, hypotonia, muscle weakness, and neonatal respiratory failure requiring ventilator support in three siblings from a consanguineous family. All exhibited perinatal fractures, and thus, a skeletal dysplasia was considered as possibly contributing to the phenotype. However, whole exome sequencing revealed a homozygous, loss-of-function pathogenic variant in LMOD3, which has recently been associated with nemaline myopathy and, in a subset of patients, perinatal fractures. This case demonstrates the importance of considering congenital neuromuscular disorders in the differential diagnosis of perinatal fractures.
杆状体肌病是一种罕见的遗传性疾病，其特征为肌无力、肌张力减退和深部腱反射减弱。它在临床和遗传方面具有异质性，最严重的表型表现为围产期运动不能、严重肌无力、喂养困难和呼吸衰竭，导致早期死亡。在受该疾病影响的患者中，已报告了12个基因的致病变异，这些基因编码肌节成分或与肌发生相关的因子。在此，我们描述了来自一个近亲家庭的三个兄弟姐妹出现的早期致死性表现，包括胎动减少、肌张力减退、肌无力和新生儿呼吸衰竭，需要呼吸机支持。所有人都出现了围产期骨折，因此，骨骼发育异常被认为可能导致了这种表型。然而，全外显子测序揭示了LMOD3基因中的一个纯合功能丧失致病变异，该变异最近已与杆状体肌病相关，并且在一部分患者中与围产期骨折有关。这个病例证明了在围产期骨折的鉴别诊断中考虑先天性神经肌肉疾病的重要性。
