The combination of congenital heart defects and vertebral anomalies with or without additional abnormalities has been reported in many genetic disorders. We describe a family in which four consecutive pregnancies were characterized by the combination of fetal congenital heart malformations and vertebral anomalies. In addition, preaxial polydactyly was detected in one of the fetuses. Reanalysis of the non-diagnostic clinical exome data revealed compound heterozygous variants c.350del, p.(Gly117AlafsTer90) and c.757G > T, p.(Asp253Tyr) in ETV2 which have previously not been known to be associated with a phenotype in humans. In mice, Etv2 encodes an obligatory transcription factor involved in the generation of hematopoietic and endothelial cells. Its homozygous disruption results in embryonic lethality due to severe blood and vessel defects. The Etv2 promoter may be bound by Nkx2-5, a key transcription factor in heart development. Pathogenic variants in the NKx2-5 homolog in humans (NKX2-5) are related to congenital heart defects. The identification of additional fetuses or live-born individuals with biallelic pathogenic variants in ETV2 will shed further light on this presumably novel gene-phenotype association and on the full phenotypic spectrum.

在许多遗传性疾病中，已有先天性心脏缺陷和椎骨异常的组合，伴有或不伴有其他异常。我们描述了一个家庭，其中四个连续怀孕的特征是胎儿先天性心脏畸形和椎骨异常的结合。另外，在其中一个胎儿中检测到了前轴多指。非诊断临床外显子组数据的再分析揭示化合物的变体的杂合c.350del，第（Gly117AlafsTer90）和c.757G> T，P。（Asp253Tyr）在ETV2其中先前没有被已知与在人类中的表型相关联的。在小鼠中，Etv2编码参与造血和内皮细胞生成的强制性转录因子。由于严重的血液和血管缺陷，其纯合破坏会导致胚胎致死。Etv2启动子可能与Nkx2-5（心脏发育中的关键转录因子）结合。在致病变种NKX2-5在人类（同源NKX2-5）都与先天性心脏缺陷。在ETV2中具有双等位基因致病变异的其他胎儿或活产个体的鉴定将为这种推测的新型基因-表型关联和完整的表型谱提供进一步的启示。