Study explores patterns of disease expression in Alagille syndrome

The nearly identical recurrent intraretinal hemorrhages observed in monozygotic twins with Alagille syndrome (ALGS) suggest a shared subclinical microvascular abnormality, according to a study.

The study hypothesizes that abnormalities in chorioretinal vascular development and/or homeostasis, rather than primary defects in neurosensory retina function, may drive the unique ophthalmic phenotypes seen in ALGS patients.

The study highlighted two monozygotic twins with Alagille syndrome, both with a heterozygous pathogenic variant in the JAG1 gene (p.Gln410Ter). The proband (P1) was diagnosed with a superficial retinal hemorrhage at age 7, which recurred 15 months later, while her twin sister (P2) experienced a retinal hemorrhage at the same location at age 11. Both had visual acuities of 20/30 in each eye and normal intravenous fluorescein angiography results. Optical coherence tomography showed thinning of the outer nuclear layer in the peripapillary retina for both, with P1’s full-field electroretinograms showing normal cone-mediated responses and P2 having normal full-field electroretinograms. Coagulation and liver function tests were normal for both twins.

The study also included the case of a 42-year-old unrelated woman with a de-novo pathogenic variant in JAG1 (p.Gly386Arg), who exhibited similar pigmentary retinopathy and hepatic vascular anomalies. Her rod and cone functions were normal across large expanses of structurally normal retina, which sharply transitioned to a blind atrophic peripheral retina.

Reference
Law C, Pattathil N, Simpson H, et al. Intraretinal hemorrhages and detailed retinal phenotype of three patients with Alagille syndrome. Ophthalmic Genet. 2024;1-10. doi: 10.1080/13816810.2024.2362214. Epub ahead of print. PMID: 38956866.

Rare Disease 360® is the Official Media Partner and Official Publication of The Alagille Syndrome Alliance (Alagille.org).