Multisystem Phenotypic Spectrum in Pediatric Heterotaxy Syndrome: A Case Series

Heterotaxy syndrome is a congenital condition characterized by abnormal left-right axis patterning of thoracoabdominal organs, frequently accompanied by complex congenital heart disease and extracardiac anomalies. The condition demonstrates considerable phenotypic variability, posing diagnostic and management challenges. We report three pediatric cases of heterotaxy syndrome classified by atrial isomerism: two with left atrial isomerism (LAI) and one with right atrial isomerism (RAI). The first case involved a 22-month-old male with LAI and polysplenia who presented with a transitional atrioventricular septal defect (AVSD), total anomalous pulmonary venous connection (TAPVC), Mobitz type II heart block, and a persistent gastrocutaneous fistula. He underwent staged surgical repair including TAPVC and AVSD correction, pulmonary valve commissurotomy, and pacemaker placement, and remained clinically stable. The second case involved a female neonate with RAI and asplenia, who presented at three weeks of age with heart failure and failure to thrive. She had complex cyanotic heart disease including double outlet right ventricle, unbalanced AVSD, TAPVC, and supraventricular tachycardia, along with extracardiac anomalies such as intestinal malrotation, gastrostomy tube dependence, and a lipomyelomeningocele. She was stabilized on medical therapy (furosemide, amlodipine, propranolol, and amoxicillin prophylaxis) and discharged home, later requiring readmission at seven months for parainfluenza infection but recovering well. At the latest follow-up, she remained clinically stable on medical management with plans for future biventricular repair. The third case involved a neonate with LAI and polysplenia who presented at birth with profound respiratory distress due to complete agenesis of the left lung, including absence of the left bronchus, pulmonary artery, and pulmonary veins, along with right pulmonary hypoplasia. Additional anomalies included a bifid right thumb. He received supportive care and was discharged on home oxygen. Genetic testing was non-diagnostic in all three patients despite extensive phenotypic abnormalities. Although the cases share hallmark features such as AVSD and abnormal pulmonary venous return, each demonstrates a distinct anatomic and clinical profile. This case series underscores the heterogeneity of heterotaxy syndrome and highlights the importance of comprehensive anatomic evaluation and multidisciplinary management.