Congenital myopathies are a genetically heterogeneous group of neuromuscular disorders that commonly present with congenital hypotonia and weakness but can also present broadly. The most severe presentation is neonatal with arthrogryposis and, rarely, fetal akinesia and pterygia, features also seen in lethal multiple pterygium syndrome (LMPS). We describe two fetuses with similar phenotype, including hydrops fetalis, large cystic hygromas, bilateral talipes, and fetal akinesia in the second trimester. Genetic diagnoses were made using exome sequencing. Both fetuses had a severe form of congenital myopathy. In the first fetus, we identified two novel compound heterozygous likely pathogenic variants consistent with autosomal recessive RYR1-related congenital myopathy (congenital myopathy 1B). In the second fetus, we identified two likely pathogenic variants, one of which is novel, likely in trans consistent with a diagnosis of autosomal recessive NEB-related congenital myopathy. Reaching a genetic diagnosis for these fetuses allowed the families to receive accurate genetic counseling for future pregnancies. These fetuses highlight the genetic and phenotypic heterogeneity of LMPS, and support a broad approach to genetic testing.

中文翻译：

---

致死性多发性翼状胬肉综合征、大囊性水瘤和腭裂：RYR1 和 NEB 相关先天性肌病的罕见且严重的胎儿表现

先天性肌病是一组具有遗传异质性的神经肌肉疾病，通常表现为先天性肌张力低下和无力，但也可能广泛存在。最严重的表现是新生儿关节弯曲，罕见的是胎儿运动不能和翼状胬肉，这些特征也见于致命性多发性翼状胬肉综合征（LMPS）。我们描述了两个具有相似表型的胎儿，包括胎儿水肿、大囊性水瘤、双侧足足和妊娠中期胎儿运动不能。使用外显子组测序进行基因诊断。两个胎儿都患有严重的先天性肌病。在第一个胎儿中，我们发现了两种新的复合杂合可能致病变异，与常染色体隐性遗传RYR1相关的先天性肌病（先天性肌病 1B）一致。在第二个胎儿中，我们发现了两种可能的致病变异，其中一种是新的，可能与常染色体隐性遗传NEB相关先天性肌病的诊断一致。对这些胎儿进行基因诊断使家庭能够为未来的怀孕获得准确的遗传咨询。这些胎儿突出了 LMPS 的遗传和表型异质性，并支持广泛的基因检测方法。