Invest Ophthalmol Vis Sci. 2021 Jun 1;62(7):27. doi: 10.1167/iovs.62.7.27.

Mariana Matioli da Palma ^1 2, Austin D Igelman ¹, Cristy Ku ¹, Amanda Burr ¹, Jia Yue You ³, Emily M Place ⁴, Nan-Kai Wang ⁵, Jin Kyun Oh ^5 6, Kari E Branham ⁷, Xinxin Zhang ⁸, Jeeyun Ahn ^9 10, Michael B Gorin ^9 11, Byron L Lam ¹², Cecinio C Ronquillo ¹³, Paul S Bernstein ¹³, Aaron Nagiel ^14 15, Rachel Huckfeldt ⁴, Michelle T Cabrera ^16 17, John P Kelly ¹⁷, Benjamin Bakall ¹⁸, Alessandro Iannaccone ⁸, Robert B Hufnagel ¹⁹, Wadih M Zein ¹⁹, Robert K Koenekoop ³, David G Birch ²⁰, Paul Yang ¹, Abigail T Fahim ⁷, Mark E Pennesi ¹

Author information

• ¹Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States.
• ²Department of Ophthalmology and Visual Sciences, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
• ³Departments of Ophthalmology, Human Genetics, and Pediatric Surgery, Montreal Children's Hospital, McGill University Health Centre, McGill University, Montreal, QC, Canada.
• ⁴Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, United States.
• ⁵Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York, New York, United States.
• ⁶State University of New York, Downstate Medical Center, Brooklyn, New York, United States.
• ⁷Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, United States.
• ⁸Duke Eye Center, Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, United States.
• ⁹UCLA Stein Eye Institute, Division of Retinal Disorders and Ophthalmic Genetics, Department of Ophthalmology, David Geffen School of Medicine, UCLA, Los Angeles, California, United States.
• ¹⁰Department of Ophthalmology, Seoul National University, College of Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
• ¹¹Department of Human Genetics, David Geffen School of Medicine, UCLA, Los Angeles, California, United States.
• ¹²Bascom Palmer Eye Institute, University of Miami, Miami, Florida, United States.
• ¹³John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States.
• ¹⁴The Vision Center, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California, United States.
• ¹⁵Roski Eye Institute, Department of Ophthalmology, University of Southern California, Los Angeles, California, United States.
• ¹⁶Department of Ophthalmology, University of Washington, Seattle, Washington, United States.
• ¹⁷Department of Ophthalmology, Seattle Children's Hospital, Seattle, Washington, United States.
• ¹⁸Department of Ophthalmology, University of Arizona College of Medicine, Phoenix, Arizon, United States.
• ¹⁹Ophthalmic Genetics and Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
• ²⁰Retina Foundation of the Southwest, Dallas, Texas, United States.

Abstract

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.