Lethal Neonatal Pulmonary Hypertension in Trisomy 21 (T21) Likely Due to Congenital Portosystemic Shunts

Children with Trisomy 21 (T21) have an increased incidence of pulmonary hypertension (PHTN); most commonly due to congenital heart/lung diseases but also in conjunction with other T21-associated gastrointestinal and metabolic abnormalities. This report describes a 2 days old, full-term male neonate with T21, without significant cardiac anomalies presenting with severe hypoxic respiratory failure eventually leading to death. Autopsy confirmed T21-associated dysmorphic features and revealed both extra and intrahepatic congenital portosystemic shunts (CPSS). Additionally, the liver demonstrated dilated hepatic and portal veins and mildly altered lobular architecture without any focal lesions. Bilateral lungs showed mild alveolar maldevelopment, double capillary loops, and normal lung to body weight ratio without vascular hypertensive changes. This case underscores the importance of careful examination of the liver hilum and considering CPSS as a potential etiology of PHTN in neonates with T21 in the absence of cardiac defects or significant lung disease.