%0 Journal Article
%T Intraretinal hemorrhages and detailed retinal phenotype of three patients with Alagille syndrome.
%A Law C
%A Pattathil N
%A Simpson H
%A Ward MJ
%A Lampen S
%A Kamath B
%A Aleman TS
%J Ophthalmic Genet
%V 0
%N 0
%D 2024 Jul 2
%M 38956866
%F 1.274
%R 10.1080/13816810.2024.2362214
%X <B>UNASSIGNED: </B>To explore patterns of disease expression in Alagille syndrome (ALGS).<BR><B>UNASSIGNED: </B>Patients underwent ophthalmic examination, optical coherence tomography (OCT) imaging, fundus intravenous fluorescein angiography (IVFA), perimetry and full-field electroretinograms (ffERGs). An adult ALGS patient had multimodal imaging and specialized perimetry.<BR><B>UNASSIGNED: </B>The proband (P1) had a heterozygous pathogenic variant in JAG1; (p.Gln410Ter) and was incidentally diagnosed at age 7 with a superficial retinal hemorrhage, vascular tortuosity, and midperipheral pigmentary changes. The hemorrhage recurred 15 months later. Her monozygotic twin sister (P2) had a retinal hemorrhage at the same location at age 11. Visual acuities for both patients were 20/30 in each eye. IVFA was normal. OCT showed thinning of the outer nuclear in the peripapillary retina. A ffERG showed normal cone-mediated responses in P1 (rod-mediated ERGs not documented), normal ffERGs in P2. Coagulation and liver function were normal. An unrelated 42-year-old woman with a de-novo pathogenic variant (p. Gly386Arg) in JAG1 showed a similar pigmentary retinopathy and hepatic vascular anomalies; rod and cone function was normal across large expanses of structurally normal retina that sharply transitioned to a blind atrophic peripheral retina.<BR><B>UNASSIGNED: </B>Nearly identical recurrent intraretinal hemorrhages in monozygotic twins with ALGS suggest a shared subclinical microvascular abnormality. We hypothesize that the presence of large areas of functionally and structurally intact retina surrounded by severe chorioretinal degeneration, is against a predominant involvement of JAG1 in the function of the neurosensory retina, and that instead, primary abnormalities of chorioretinal vascular development and/or homeostasis may drive the peculiar phenotypes.