David Chitayat

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 RRS 3 . 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.

Autosomal recessive microcephaly and chorioretinopathy‐1 (MCCRP1) is a rare Mendelian disorder resulting from biallelic loss of function variants in Tubulin‐Gamma Complex Associated Protein 6 ( TUBGCP6 , MIM#610053). Clinical features of this disorder include microcephaly, cognitive impairment, dysmorphic features, and variable ophthalmological anomalies including chorioretinopathy. Microcephaly can be recognized prenatally and visual impairment becomes evident during the first year of life. The clinical presentation resembles the findings in some acquired conditions such as congenital toxoplasmosis and cytomegalovirus infections; thus, it is important to recognize and diagnose this syndrome in view of its impact on patient health management and familial reproductive plans. To date, only seven molecularly confirmed patients from five unrelated families have been reported. We report an additional four unrelated patients with TUBGCP6 variants including one prenatal diagnosis and review the clinical phenotypes and genotypes of all the known cases. This report expands the molecular and phenotypic spectrum of TUBGCP6 and includes additional prenatal findings associated with MCCRP1.