First Prenatal Report of Ververi–Brady Syndrome: From Fetal Clues to Genetic Truth!

BACKGROUND: Exome sequencing in fetal increased nuchal translucency is still debated upon- however it is able to detect rare disease causing genetic mutations especially those that are associated with neurodevelopmental delay. Mutations in neurodevelopmental genes are the main actionable genetic variations during prenatal testing, as they lead to significant lifelong disability and are not treatable. Ververi-Brady syndrome (VEBRAS) is a recently described neurodevelopmental syndrome with associated facial dysmorphology, first reported in 2018. CASE: A 34-year-old primigravida at 12 weeks' gestation had fetal nuchal translucency measuring between the 95th to 99th centile with a low combined risk for the common aneuploidies. Early anomaly scan at 17 + 4 weeks showed resolving nuchal fold thickness, but with suboptimal fetal growth (12th centile) and echogenic bowel. An amniocentesis was performed and the Whole exome Sequencing revealed a mutation in Exon 3 of QRICH1 gene, associated with VEBRAS. A review scan at 23 weeks showed suboptimal fetal growth (5th centile), echogenic bowel, facial dysmorphism and delayed sulcations. Parental genetic testing was suggestive of a de novo mutation in the fetus. CONCLUSION: High throughput genome wide tests like Exome sequencing may detect non-specific genetic variations but when used judiciously at a specialist fetal medicine and genetic center, it is an excellent technology for detection and prevention of rare untreatable genetic conditions. Exome sequencing can facilitate prenatal diagnosis of rare genetic disorders such as VEBRAS; however, counseling remains challenging because the degree of neurodevelopmental involvement cannot be accurately predicted from prenatal findings alone.