Discussion

Transposition of the great arteries accounts for 5–7% of all CHDs and remains the most common cyanotic CHD presenting in the neonatal period. Its pathogenesis has been traditionally considered sporadic and idiopathic, with low familial recurrence and few known genetic associations. ^{Reference Chhatwal, Smith, Bola, Zahid, Venkatakrishnan and Brand1,Reference Morton, Quiat, Seidman and Seidman2} However, emerging literature increasingly suggests that a subset of cases may have a genetic or familial basis. ^{Reference Postma, Bezzina and Christoffels3,Reference Morrish, Smith and Enriquez4}

In a large prospective multicentre study, Digilio et al. evaluated 370 patients with nonsyndromic complete transposition of the great arteries and found that 10% had relatives with CHD, including concordant transposition of the great arteries or congenitally corrected transposition of the great arteries in 11 families. ^{Reference Digilio, Casey and Toscano5} These findings challenge the traditional classification of transposition of the great arteries as a purely sporadic anomaly and suggest possible monogenic or oligogenic inheritance in certain kindreds. Our report further strengthens this hypothesis. The presence of concordant dextro-transposition of the great arteries in both of our patients, combined with their shared placentation and presumably identical genetic background, supports the notion of a heritable predisposition, possibly involving genes related to conotruncal septation, cardiac looping, or left–right patterning.

In a recent case series by Hu et al., only one of three twin pregnancies with transposition of the great arteries involved monochorionic diamniotic twins, and in all instances only one twin was affected. ^{Reference Hu, Deng and Zhu6} In a retrospective analysis of all twin pairs undergoing fetal echocardiography at a single institution, among the 23 monochorionic twin pairs having CHD, 18 pairs had discordant CHD and only 5 pairs had concordant CHD, supporting the role of environmental and epigenetic influences. ^{Reference Imany-Shakibai, Yin, Russell, Sklansky, Satou and Afshar7} In the study by Diglio et al., involving non-syndromic transposition of the great arteries patients, three patients had an unaffected monozygotic twin. ^{Reference Digilio, Casey and Toscano5}

The phenotypic similarity in cardiac morphology between the two twins—both having transposition of the great arteries with mid-apical muscular ventricular septal defects—also points towards disruption of a shared developmental pathway. However, the coronary pattern was different. Although the timing and outcomes differed significantly between the two, the fundamental lesion was essentially concordant. Such late clinical presentation of the heart condition could be influenced by modifying genetic, epigenetic, or environmental factors.

This case also highlights the clinical importance of considering familial recurrence in CHD. Current guidelines do not mandate routine cardiac screening for siblings in twin pregnancies. ^{Reference Lopez, Saurers and Barker8} However, in the context of shared placentation and a diagnosis of dextro-transposition of the great arteries in one sibling, early screening echocardiography in the co-twin could enable timely diagnosis and intervention. In our case, earlier identification might have allowed earlier referral and surgical repair for the second twin, potentially mitigating complications.

While our case supports the need for routine postnatal cardiac screening in monochorionic twins when one is affected, it also underscores the value of offering genetic counselling and testing to such families. Although our patient’s family declined genetic analysis, identifying mutations in genes known to influence cardiac development could contribute valuable insights into the genetic architecture of transposition of the great arteries.