The concordance rate of non-chromosomal congenital malformations in twins based on zygosity: a retrospective cohort study

Objective: To examine the concordance rate of non-chromosomal congenital malformations in twin pairs based on zygosity. Design: Retrospective cohort study. Setting: A tertiary hospital in Korea. Population: Twin pairs born at Seoul National University Hospital between 2001 and 2019. Methods: Congenital malformations were diagnosed by postnatal workups of neonates or autopsy in cases of stillborn infants. Zygosity was confirmed by sex, chorionicity and DNA analysis. Main outcome measures: Concordance rate of congenital malformations in twin pairs based on zygosity. Results: In total, 3386 twin pairs were included. The risk of a congenital malformation in the index twin increased significantly if the co-twin had the congenital malformation, and the concordance rate was higher in monozygotic (MZ) than in dizygotic (DZ) twins (37.04 versus 16.77, P < 0.001). An increased risk of a congenital malformation in the presence of the same congenital malformation in the co-twin was observed only for malformations of the nervous system, eye/ear/face/neck, circulatory system, cleft lip/palate, genital organs, urinary system and musculoskeletal system. Significantly higher concordance rates in MZ than in DZ twin pairs were observed only for the nervous system (40.00 versus 0.00, P < 0.001), circulatory system (32.97 versus 19.74, P = 0.021), cleft lip/palate (44.44 versus 0.00, P = 0.017) and urinary system (22.22 versus 0.00, P = 0.004), whereas significant differences were not found for the genital organs or musculoskeletal system. Conclusions: Monozygotic twins had higher concordance rates than DZ twins only in specific organ systems. It may be speculated that nervous system, circulatory system, cleft lip/palate and urinary system are primarily genetically affected. Tweetable abstract: Monozygotic twins had higher concordance rates than dizygotic twins only in specific organ systems.