Prenatal diagnosis of ROR‐2 related Robinow syndrome presenting with fetal ultrasound findings of mesomelia, vertebral, digital and genital abnormalities

Autosomal recessive ROR2‐Robinow syndrome is caused by pathogenic variants in the ROR2 gene. Fetal ultrasound done on our patient at 24 + 3/7 weeks gestation showed macrocephaly, brachycephaly, flat face, prominent forehead, mild frontal bossing, lower thoracic hemivertebrae, digital abnormalities and micropenis. Fetal trio whole exome sequencing done on amniocytes showed two pathogenic compound heterozygous variants in the ROR2 gene, c.1324 C > T; p.(Arg442*) maternally inherited and c.1366dup; p.(Leu456Profs*3) apparently de novo. c.1324 C > T; p.(Arg442*) is a nonsense variant resulting in protein truncation reported to be associated with RRS3. c.1366dup; p.(Leu456Profs*3) is a frameshift variant predicted to result in protein truncation reported to segregate with the disease in multiple affected individuals from a single large family with distal symphalangism of the fourth finger. Fetal autopsy following pregnancy termination showed a large head with low‐set ears, facial abnormalities, mesomelic bone shortening, hemivertebra, fused S3 and S4 vertebral bodies, several fused rib heads and short penis with buried shaft. Key points What is already known about this topic? Autosomal recessive ROR2‐Robinow syndrome (RRS) is caused by pathogenic variants in the ROR2 gene. The prenatal phenotype of fetuses with RRS includes a prominent forehead, hypertelorism, mesomelia, hemivertebrae, rib and vertebral fusion, hand and foot malformations and hypoplastic external genitalia. What does this study add? We describe a case in which RRS was suspected based on comprehensive prenatal phenotyping and confirmed on molecular testing. RRS should be considered when ultrasound suggests a non‐lethal skeletal dysplasia with vertebral, digital and male genital abnormalities.