Abstract：
Due to abnormal prenatal ultrasound findings of femoral shortening and flattened facial profile, a G2P0 pregnant patient underwent an amniocentesis at 15 weeks of gestation for proband-only exome sequencing. Bioinformatic filtering for genes included on the laboratory\'s extended skeletal dysplasia panel identified a heterozygous, likely pathogenic, frameshift variant in DVL1 NM_001330311.2:c.1575_1582dup; (p.Pro528ArgfsTer149). Pathogenic variants in DVL1 are associated with autosomal dominant Robinow syndrome (ADRS), a genetic disorder characterized by skeletal dysplasia with genital and craniofacial abnormalities. Prenatal ultrasound in the third trimester noted shortened long bones (first percentile for gestational age), macrocephaly with frontal bossing, short and upturned nose with a wide nasal root, triangular mouth, low pedal arches concerning for rocker-bottom feet, and ambiguous genitalia. A postnatal exam by Medical Genetics confirmed the prenatal findings in addition to hypertelorism, brachydactyly with broad thumbs and halluces, clinodactyly of second fingers, rigid gums with a frontal frenulum, and a sacral dimple. This case describes a novel variant in DVL1 identified in a fetus with prenatal and postnatal phenotypic features consistent with ADRS. To our knowledge, this is the first reported case of a prenatal molecular diagnosis of the dominant form of Robinow syndrome and the third case to describe prenatal ultrasound findings associated with this diagnosis.
摘要：
由于产前超声检查发现股骨缩短和面部扁平，1例G2P0妊娠患者在妊娠15周时进行羊膜穿刺术,以仅先证者外显子组测序.实验室的扩展骨骼发育不良组中包含的基因的生物信息学过滤鉴定出杂合，可能致病，DVL1NM_001330311.2中的移码变体：c.1575_1582dup；（第Pro528ArgfsTer149）。DVL1的致病变异与常染色体显性Robinow综合征（ADRS）有关，一种以骨骼发育不良伴生殖器和颅面异常为特征的遗传性疾病。妊娠晚期的产前超声检查注意到长骨缩短（胎龄的第一百分位数），大头畸形伴额头突出，短而上翘的鼻子，鼻根宽，三角嘴,关于摇杆底脚的低踏板拱门，还有模棱两可的生殖器.医学遗传学的产前检查证实了产前发现，矮胖的拇指和幻觉，第二个手指倾斜，带有额骨系带的坚硬牙龈，还有一个骶骨酒窝.该病例描述了在胎儿中发现的DVL1的新变体，其产前和产后表型特征与ADRS一致。据我们所知,这是报道的首例主要形式Robinow综合征的产前分子诊断病例,也是描述与该诊断相关的产前超声检查结果的第三例病例.
