Alagille Syndrome

Few patients meet classical diagnostic criteria for ALGS without genetic analysis

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Genetic testing is a significant factor in facilitating early and accurate diagnosis of Alagille syndrome (ALGS), according to a study.

Researchers studied 18 patients who presented with cholestasis, a common symptom of ALGS. To identify potential genetic causes, the researchers employed a Next-Generation Sequencing (NGS) panel targeting coding exons of 52 genes, which included the JAG1 and NOTCH2 genes. The identified mutations were then confirmed through Sanger sequencing in both affected individuals and their family members.

The findings revealed that the typical facial phenotype associated with ALGS was observed in 16 out of 18 patients (88.9%). Additionally, 44.4% of patients displayed heart defects, with pulmonary stenosis being the most common cardiac abnormality. Furthermore, butterfly vertebrae, a skeletal anomaly, were seen in 35.7% of the cases. Renal involvement was detected in 11.1% of patients, with 1 patient presenting renal cysts and another with obstructive hydronephrosis.

An ophthalmology examination was performed on 12 children, and only 1 child exhibited posterior embryotoxon (8.3%), a characteristic eye abnormality associated with ALGS.

A percutaneous liver biopsy was conducted in 9 cases, with 6 of them showing bile duct paucity (66.7%). Liver transplantation was required in 2 patients due to the progression of cirrhosis.

The genetic analysis led to the identification of 9 novel variants in the JAG1 gene, consisting of 8 frameshift variants and 1 missense variant. None of the patients exhibited NOTCH2 variants.

The study found that only 6 patients could meet the classical diagnostic criteria for ALGS without genetic analysis.

Semenova N, Kamenets E, Annenkova E, et al. Clinical Characterization of Alagille Syndrome in Patients with Cholestatic Liver Disease. Int J Mol Sci. 2023;24(14):11758. doi: 10.3390/ijms241411758. PMID: 37511516; PMCID: PMC10380973.