EP18.25: Exome sequencing reveals patterns in recurrent isolated fetal anomalies: insights from three case reports

Prenatal exome sequencing, recommended by the International Society for Prenatal Diagnosis for cases of recurrent fetal anomalies with suspected genetic origins, offers a transformative approach to diagnosis and genetic understanding. We present three intriguing cases where exome sequencing identified underlying gene mutations in recurrent isolated fetal anomalies detected via ultrasound. In the first case, recurrent isolated microcephaly was detected at the 18th week of gestation. Clinical exome sequencing pinpointed pathogenic mutations (c.7324C>T, p.Arg2442Ter) and likely pathogenic mutations (c.10148 delC) in the ASPM gene, associated with autosomal recessive forms of microcephaly. The second case involved recurrent isolated hydrocephalus observed at the 22nd week of gestation. Exome sequencing identified mutations in the MPDZ gene (c.3508C>T, p.Arg1170Ter and c.1197dup, p.Leu400fs) linked to autosomal-recessive congenital hydrocephalus. The third case revealed recurrent isolated fetal omphalocele detected at the 15th gestational week. Exome sequencing uncovered a mutation in the CDKN1C gene (c.835C>T, p.Arg279Cys), associated with Beckwith-Wiedemann syndrome, a rare overgrowth disorder characterised by omphalocele among other clinical features. These cases underscore the pivotal role of exome sequencing in unravelling the genetic basis of recurrent fetal anomalies detected by prenatal ultrasound. Prioritising genetic investigation is crucial for precise diagnosis, risk assessment, and informed genetic counselling, thus advancing prenatal care and clinical management.