Abstract：
Skeletal dysplasias (SDs) are a large, heterogeneous group of mostly genetic disorders that affect the bones and cartilage, resulting in abnormal growth and development of skeletal structures. The high clinical and genetic diversity in SDs cause difficulties in prenatal diagnosis. To establish a correct prognosis and better management, it is very important to distinguish SDs with poor life-limiting prognosis or lethal SDs from other ones. Bad prognosis in foetuses is assessed on the basis of the size of the thorax, lung volumes, long bones’ length, bones’ echogenicity, bones’ angulation or presented fractures, and the concomitant presence of non-immune hydrops or visceral abnormalities. To confirm SD diagnosis and perform family genetic consultation, rapid molecular diagnostics are needed; therefore, the NGS method using a panel of genes corresponding to SD or whole-exome sequencing (WES) is commonly used. We report a case of a foetus showing long bones’ shortening and a narrow chest with short ribs, diagnosed prenatally with asphyxiating thoracic dystrophy, also known as Jeune syndrome (ATD; OMIM 208500), caused by compound heterozygous variants in the DYNC2H1 gene, identified by prenatally performed rapid-WES analysis. The missense variants in the DYNC2H1 gene were inherited from the mother (c.7289T>C; p.Ile2430Thr) and from the father (c.12716T>G; p.Leu4239Arg). The DYNC2H1 gene is one of at least 17 ATD-associated genes. This disorder belongs to the ninth group of SD, ciliopathies with major skeletal involvement. An extremely narrow, bell-shaped chest, and abnormalities of the kidneys, liver, and retinas were observed in most cases of ATD. Next to lethal and severe forms, clinically mild forms have also been reported. A diagnosis of ATD is important to establish the prognosis and management for the patient, as well as the recurrence risk for the family.
摘要：
骨骼发育不良(SD)是一个很大的，影响骨骼和软骨的主要是遗传性疾病的异质性组，导致骨骼结构的异常生长和发育。SDs的高临床和遗传多样性导致产前诊断困难。建立正确的预后和更好的管理，将具有不良寿命限制预后的SDs或致死性SDs与其他SDs区分开来非常重要.胎儿的不良预后是根据胸部的大小来评估的，肺容量,长骨的长度，骨头的回声，骨头成角度或出现骨折，以及伴随的非免疫性水肿或内脏异常的存在。确认SD诊断并进行家族遗传咨询，需要快速分子诊断；因此，通常使用使用对应于SD或全外显子组测序(WES)的一组基因的NGS方法。我们报告了一例胎儿，显示长骨缩短，胸部狭窄，肋骨短，产前诊断为窒息性胸廓营养不良,也称为Jeune综合征（ATD；OMIM208500），由DYNC2H1基因中的复合杂合变体引起，通过产前进行的快速WES分析鉴定。DYNC2H1基因中的错义变体遗传自母亲(c.7289T>C;p.Ile2430Thr)和父亲(c.12716T>G;p.Leu4239Arg)。DYNC2H1基因是至少17种ATD相关基因之一。这种疾病属于SD的第九组，主要骨骼受累的纤毛病。一个极其狭窄的，钟形胸部,和肾脏的异常，肝脏,在大多数ATD病例中观察到视网膜。除了致命和严重的形式，临床上温和的形式也有报道。ATD的诊断对于确定患者的预后和管理非常重要。以及家庭复发的风险。
