Genetic Analysis in Monochorionic Diamniotic Twins Discordant for One Fetus With Structural Anomalies

OBJECTIVE: Data concerning the prenatal diagnostic value of exome sequencing (ES) for twins with structural anomalies remain limited. Therefore, this study aimed to investigate the genetic etiology of monochorionic diamniotic (MCDA) twins discordant for one fetus with structural anomalies and assess the incremental diagnostic yield of chromosomal microarray analysis (CMA) and ES. METHODS: This single-center retrospective study included 170 MCDA twin pregnancies in which one fetus exhibited structural anomalies between December 2012 and July 2023. Both twins underwent genetic testing using karyotyping, CMA, and/or Trio-ES. Since 2021, Beckwith-Wiedemann syndrome (BWS) testing has been performed in patients with exomphalos and negative ES results. RESULTS: Aneuploidy was identified in 8.2% (14/170) of MCDA twin pairs. CMA and Trio-ES provided incremental diagnostic yields of 0.6% (1/160) and 7.1% (3/42), respectively. BWS was confirmed in two fetuses presenting with exomphalos. Abnormal genetic results were detected in only one fetus in 13 cases, including 11 with aneuploidy and two with BWS. Genetic disorders were identified in both fetuses in seven cases, including three with aneuploidy, one with a pathologic copy number variant, and three with causative variants. Discordant genetic results between the twins were observed in 8.8% (15/170) of the cases. Hydrops fetalis and multisystem anomalies were correlated with a higher incidence of genetic disorders. CONCLUSION: Invasive diagnostic testing should be considered for both twins when one fetus in an MCDA pregnancy presents with structural anomalies. Although CMA offers a limited additional yield, ES improves the detection rate and should be considered for the comprehensive genetic evaluation of MCDA twins discordant for structural anomalies.