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Alagille syndrome is caused by mutations in genes involved in NOTCH signaling, specifically JAG1 and NOTCH2, and is associated with a high rate of peripheral pulmonary artery stenosis. In this study, we report the case of an infant with Alagille syndrome caused by a JAG1 mutation, who succumbed to acute exacerbation of right heart failure due to severe peripheral pulmonary artery stenosis. The autopsy revealed that the peripheral pulmonary arteries were significantly stenosed, exhibiting hypoplasia and thickened vessel walls. Histological examination of the pulmonary artery walls showed a decrease in smooth muscle cells in the tunica media and an increase in collagen and elastic fibers, although the intrapulmonary arteries were intact. These findings are important for understanding the pathogenesis of Alagille syndrome and developing treatment strategies for peripheral pulmonary artery stenosis., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Peripheral pulmonary artery stenosis (PPAS) is a rare form of congenital heart disease that is most frequently associated with Williams and Alagille syndromes. These patients typically have systemic level right ventricular pressures secondary to obstruction at the lobar, segmental, and subsegmental branches. The current management of patients with PPAS remains somewhat controversial. We have pioneered an entirely surgical approach for the reconstruction of PPAS. This approach initially entailed a surgical patch augmentation of all major lobar branches and effectively reduced the right ventricular pressures by more than half. This was the first report demonstrating an effective approach to this disease. Over the past 5 years, we have gradually evolved our technique of reconstruction to include segmental and subsegmental branch stenoses. An important technical aspect of this approach entails the division of the main pulmonary and separation of the branch pulmonary arteries to access the lower lobe branches. Pulmonary artery homograft patches are used to augment hypoplastic pulmonary artery branches. In addition, we perform a Heinecke-Miculicz-type ostioplasty for isolated ostial stenoses. The technical details of the surgical approach to PPAS are outlined in this article and can also be used for other complex peripheral pulmonary artery reconstructions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Alagille syndrome (ALGS) is an autosomal dominant disorder associated with cholestatic liver disease, pulmonary valvar stenosis or atresia, vasculopathy, and renal disease. Although the liver and cardiac manifestations contribute to overall morbidity and mortality during their life span, these patients also carry a burden of important but often underappreciated vascular abnormalities. This report describes a 3 year-old girl with Alagille syndrome, hepatic cholestasis, systemic hypertension, hypercholesterolemia, hypertriglyceridemia, and tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collaterals (TOF/PA/MAPCAs). She presented for bilateral pulmonary artery plasty and central shunt upsizing. She then experienced three shunt dehiscence episodes, necessitating emergent intervention. Autopsy showed diffuse atherosclerosis and significant atherosclerotic plaque at the site of shunt dehiscence. This is the first reported case of ALGS with TOF/PA/MAPCAs and catastrophic shunt dehiscence due to significant generalized vasculopathy caused by dyslipidemia and atherosclerosis. Dyslipidemia, a known comorbidity in ALGS, is one of few modifiable risk factors that should be screened for and treated, particularly before cardiac surgery.

Alagille syndrome is a dominantly inherited multisystem disorder involving multiple organs including the liver, heart, eyes, face, and skeleton. Congenital heart defects, the majority of which are right-sided, contribute significantly to the mortality of these patients. We report a patient with Alagille syndrome who presented with mitral valve regurgitation requiring valvuloplasty and subsequent mitral valve replacement. The patient was ultimately diagnosed with anomalous origin of the left coronary artery from the pulmonary artery and underwent successful reimplantation.

We described a case of Alagille syndrome with severe peripheral pulmonary artery stenosis and very high right ventricular pressure that underwent successful living-related liver transplantation without any peri-operative and mid-term postoperative complication because of this cardiac malformation. The aim of this report is to point out that the severe pulmonary artery stenosis may be a risk factor but not a contraindication to liver transplantation in patients with Alagille syndrome.