The multiple pterygium syndromes (MPS) are rare disorders with disease severity ranging from lethal to milder forms. The nonlethal Escobar variant MPS (EVMPS) is characterized by multiple pterygia and arthrogryposis, as well as various additional features including congenital anomalies. The genetic etiology of EVMPS is heterogeneous and the diagnosis has been based either on the detection of pathogenic CHRNG variants (~23% of patients), or suggestive clinical features. We describe four patients with a clinical suspicion of EVMPS who manifested with multiple pterygia, mild flexion contractures of several joints, and vertebral anomalies. We revealed recessively inherited MYH3 variants as the underlying cause in all patients: two novel variants, c.1053C>G, p.(Tyr351Ter) and c.3102+5G>C, as compound heterozygous with the hypomorphic MYH3 variant c.‐9+1G>A. Recessive MYH3 variants have been previously associated with spondylocarpotarsal synostosis syndrome. Our findings now highlight multiple pterygia as an important feature in patients with recessive MYH3 variants. Based on all patients with recessive MYH3 variants reported up to date, we consider that this disease entity should be designated as “Contractures, pterygia, and variable skeletal fusions syndrome 1B,” as recently suggested by OMIM. Our findings underline the importance of analyzing MYH3 in the differential diagnosis of EVMPS, particularly as the hypomorphic MYH3 variant might remain undetected by routine exome sequencing.

中文翻译：

---

隐性MYH3变异体导致模仿Escobar变异体多发性翼状syndrome肉综合征的“挛缩症，翼状gia肉和可变性骨骼融合综合征1B”。

多发性翼状syndrome肉综合征（MPS）是罕见疾病，其严重程度从致死性到轻度形式不等。非致命性Escobar变体MPS（EVMPS）的特征是多发性翼状and肉和关节变态，以及包括先天性异常在内的各种其他特征。EVMPS的遗传病因是异质的，诊断基于发现病原性CHRNG变体（约23％的患者）或具有暗示性的临床特征。我们描述了四例临床怀疑为EVMPS的患者，这些患者表现为多发性翼状，肉，几个关节的轻度屈曲挛缩和椎骨异常。我们揭示了隐性遗传的MYH3变体是所有患者的潜在病因：两个新的变体c.1053C> G，p。（Tyr351Ter）和c.3102 + 5G> C，与亚型MYH3变体c.-9 + 1G> A复合杂合。隐性MYH3变体先前已与脊椎腕骨滑膜综合症相关。我们的发现现在强调多发性翼状pt肉是隐性MYH3变异患者的重要特征。根据最新报道的所有具有隐性MYH3变异的患者，我们认为该疾病实体应指定为“合同，翼状，肉和可变骨骼融合综合征1B”，如OMIM最近建议的那样。我们的发现强调了分析MYH3的重要性在EVMPS的鉴别诊断中，特别是因为亚型MYH3变异可能无法通过常规外显子组测序检测到。