Characterization of the Spectrum of Ophthalmic Changes in Patients With Alagille Syndrome

PURPOSE. The purpose of this study was to characterize the phenotypic spectrum of ophthalmic findings in patients with Alagille syndrome. METHODS. We conducted a retrospective, observational, multicenter, study on 46 eyes of 23 subjects with Alagille syndrome. We reviewed systemic and ophthalmologic data extracted from medical records, color fundus photography, fundus autofluorescence, optical coherence tomography, visual fields, electrophysiological assessments, and molecular genetic findings. RESULTS. Cardiovascular abnormalities were found in 83% of all cases (of those, 74% had cardiac murmur), whereas 61% had a positive history of hepatobiliary issues, and musculoskeletal anomalies were present in 61% of all patients. Dysmorphic facies were present in 16 patients, with a broad forehead being the most frequent feature. Ocular symptoms were found in 91%, with peripheral vision loss being the most frequent complaint. Median (range) Snellen visual acuity of all eyes was 20/25 (20/20 to hand motion [HM]). Anterior segment abnormalities were present in 74% of the patients; of those, posterior embryotoxon was the most frequent finding. Abnormalities of the optic disc were found in 52%, and peripheral retinal abnormalities were the most frequent ocular finding in this series, found in 96% of all patients. Fifteen JAG1 mutations were identified in 16 individuals; of those, 6 were novel. CONCLUSIONS. This study reports a cohort of patients with Alagille syndrome in which peripheral chorioretinal changes were more frequent than posterior embryotoxon, the most frequent ocular finding according to a number of previous studies. We propose that these peripheral chorioretinal changes are a new hallmark to help diagnose this syndrome.

Automated summary

This study aimed to characterize the phenotypic spectrum of ophthalmic findings in patients with Alagille syndrome. It found that cardiovascular abnormalities, hepatobiliary issues, musculoskeletal anomalies, dysmorphic facies, peripheral vision loss, anterior segment abnormalities, optic disc abnormalities, and peripheral retinal abnormalities were common in these patients. It also identified novel JAG1 mutations in some individuals, suggesting the potential for new diagnostic markers for this syndrome.