Peripheral chorioretinal atrophy may have diagnostic value in older children and adults with Alagille syndrome (ALGS).
Researchers at the Casey Eye Institute in Oregon Health & Science University (OHSU) observed “a characteristic peripheral chorioretinal degeneration that correlates with loss of function in the visual field” and that these “posterior changes in the periphery were more common than posterior embryotoxon, an asymptomatic and classic feature.”
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The retrospective, multicenter study comprising 46 eyes from 11 male and 12 female subjects (median age at the last ophthalmologic follow-up, 16 years, range 3-52 years) found ocular symptoms in 91% of the ALGS patients.
Abnormalities in the posterior segment were more common than in the anterior segment (96% vs 74%), with peripheral retinopathy being the most prevalent ocular finding (96%). Wide‑field autofluorescence studies showed well-demarcated areas of peripheral chorioretinal atrophy that involved both eyes symmetrically. Rod-cone dysfunction was observed in 82% of the patients who underwent electroretinography, while isolated rod dysfunction was found in 12%.
Additional posterior segment abnormalities included optic disc defects (52%) and macular changes (78%). Posterior embryotoxon was the main alteration in the anterior segment (70%), followed by minor fractions of iris stromal hypoplasia (22%) and bilateral cataracts (17%), particularly of the posterior subcapsular type.
The spectrum of ophthalmologic symptoms also included decreased peripheral vision issues (15/22), nyctalopia (11/23), and photophobia (8/23).
Out of the 23 patients, 19 presented cardiovascular issues, including heart murmur (74%), the most common extra-ocular finding, pulmonary artery stenosis (53%), and ventricular septal defect (26%). Most patients also presented hepatobiliary and musculoskeletal abnormalities (61%). Dysmorphic facies were detected in 16 patients, in particular broad forehead (88%), deep-set eyes (69%), straight nose (56%), and pointed chin (56%).
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The molecular profiling identified Jagged1 (JAG1) mutations in 16 of the patients with conclusive genetic testing. Most of them resulted in the introduction of premature stop codons in JAG1’s sequence. Six novel JAG1 variants were reported, including 2 nonsense and 4 frameshift variants. None of the patients presented Notch2 (NOTCH2) mutations.
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Future longitudinal studies could unveil the occurrence of progressive chorioretinal atrophy with loss of visual field in ALGS patients.
da Palma MM, Igelman AD, Ku C, et al. Characterization of the spectrum of ophthalmic changes in patients with Alagille syndrome. Investig Ophthalmology Vis Sci. 2021;62(7):27. doi:10.1167/iovs.62.7.27