Physicians reported on the cases of 2 patients with Alagille syndrome (ALGS) with novel JAG1 gene mutations who presented with cholestasis.

The report, as detailed in Frontiers in Pediatrics, highlights the importance of distinguishing infants with biliary atresia from those with ALGS as early as possible.

The first patient was a 1-month-old infant girl who presented with yellowish sclera discoloration and light-colored stools. Upon examination, she was discovered to have an inverted triangular face with a high prominent forehead and pointed chin, deep set eyes, and a bulbous nose tip. 

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Chest X-ray revealed butterfly vertebrae. A hepatobiliary ultrasound scan did not show any abnormalities in the liver or the bile ducts. Computed tomographic angiography demonstrated that the patient had right and left pulmonary artery stenosis and persistent left superior vena cava. Liver function tests revealed abnormally high bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and gamma-glutamyl transferase levels (GGT). 

Read more about Alagille syndrome etiology 

Laparoscopic biliary exploration, cholangiography, and liver biopsy were carried out on day 10 of admission. The intrahepatic bile ducts could be visualized, ruling out biliary atresia. Genetic testing was conducted to verify suspicions of Alagille syndrome; a nonsense variant in the JAG1 gene was identified via cholestasis-related gene sequencing. 

The initiation of treatment allowed the child’s liver function tests to normalize and resolved her jaundice. 

The second patient was a 1-month-old infant boy who also presented with yellowish skin, sclera discoloration, and light-colored stools. Both he and his mother appeared to have the craniofacial dysmorphism typically seen in those with Alagille syndrome. 

Cardiac ultrasound revealed increased flow velocity in the aorta and descending aortic arch, as well as in the left and right pulmonary arteries. Mild tricuspid regurgitation was also detected. Renal ultrasound revealed an increased resistance index in both renal arteries. 

Hepatobiliary ultrasound did not show any abnormalities in the liver and the bile ducts. Liver function tests revealed that he had high bilirubin, alanine aminotransferase (ALT), AST, GGT, ALP, triglyceride, and total cholesterol levels.

Read more about Alagille syndrome treatment

A laparoscopic biliary exploration, cholangiography, and liver biopsy were conducted on day 6 of admission, which ruled out biliary atresia. Genetic testing revealed a frameshift variant in the JAG1 gene. After 9 months of treatment, his liver function test remained deranged and he was still visibly jaundiced. He is now awaiting liver transplantation.

“We report two cases of infants with Alagille syndrome in which biliary atresia was ruled out by comprehensive examination,” the authors wrote. “Broadening the mutational spectrum may help geneticists to better identify etiologic mutations that cause Alagille syndrome.” 


Han Y, Zhu K, Wu H, et al. Case report: novel JAG1 gene mutations in two infants with Alagille syndrome characterized by cholestasisFront Pediatr. 2022;10:1017647. doi:10.3389/fped.2022.1017647