P2A153: A Neonatal Case of Vascular Ring with Alagille Syndrome

Introduction: A term infant was prenatally diagnosed with a right aortic arch with vascular ring. Infant was clinically found to have features consistent with Alagille Syndrome (ALGS). Our geneticist observed that the healthy patient’s mother had similar facial features. Both were diagnosed with ALGS, with the same heterozygous JAG1 gene (NM_000214.2) variant (c.1890_1893del, p.Ile630Metfs*112). We believe our patient’s vascular ring is the first reported vascular ring associated with ALGS.

Case Description: A 37 week 5 days old female infant was prenatally diagnosed with a right aortic arch with vascular ring. Postnatal echo showed a right aortic arch with aberrant left subclavian artery and left sided ductus arteriosus (forming a vascular ring) and a small VSD. On day of life 3, the infant appeared bronze grey in color and found to have cholestasis.

Abodminal ultrasound revealed 2 right renal arteries. A butterfly vertebra was noted at T6. Ophthalmology exam revealed bilateral posterior embryotoxon. MRA brain showed markedly hypoplastic bilateral internal carotid arteries which did not appear to reach the level of the skull base. The anterior circulation was fed by the posterior circulation through prominent communicating arteries.

Infant’s facial features were consistent with ALGS. The patient’s mother had similar facial features. A cholestasis genetic panel confirmed Alagille syndrome due to a heterozygous JAG1 gene mutation (NM_000214.2) variant (c.1890_1893del, p.Ile630Metfs*112).

Discussion: ALGS is an autosomal dominant syndrome with variable penetrance affecting multiple organs: liver, kidney, heart and blood vessels, skeleton, and eyes.

Cardiovascular anomalies occur in more than 90% of ALGS patients. The majority of patients have cardiovascular anomalies with reports between 81% and 100% being affected. The most common complex congenital defect is Tetralogy of Fallot which accounts for 7-12% and pulmonary stenosis/hypoplasia is the most frequent simple defect. In a large study, up to 22% of patients had right-sided congenital heart defects, 11% with left-sided congenital heart disease, and 15% with atrial or ventricular septal defects. Our patient had a VSD and a right aortic arch. There have also been other reports of right aortic arch anomalies but we were unable to find other cases of a vascular ring.

The most common cardiac defect is peripheral pulmonary stenosis affecting at least 75% of cases. It has been described that 10% of Alagille patients have other blood vessel anomalies including stenoses which may involve intracranial vessels, the aorta, and renal, celiac, superior mesenteric and subclavian arteries. There have been reports of Alagille cases with an aberrant subclavian, sometimes hypoplastic. Our patient’s hypoplastic internal carotid arteries, duplicate right renal arteries, aberrant left subclavian artery, and left-sided ductus arteriosus forming a vascular ring all represent regional vessel involvement associated with Alagille syndrome.

Conclusion: We believe our patient’s vascular ring is the first reported vascular ring associated with ALGS.