Intraretinal hemorrhages and detailed retinal phenotype of three patients with Alagille syndrome.

Autor:	Law C; Queen's University School of Medicine, Kingston, Ontario, Canada.; Department of Ophthalmology, Queen's University and Kingston Health Sciences Centre, Kingston, Canada., Pattathil N; Queen's University School of Medicine, Kingston, Ontario, Canada., Simpson H; Department of Ophthalmology, Queen's University and Kingston Health Sciences Centre, Kingston, Canada., Ward MJ; Division of Ophthalmology, Department of Surgery, Chester County Hospital and Chester County Eye Care Associates, West Chester, Pennsylvania, USA., Lampen S; Queen's University School of Medicine, Kingston, Ontario, Canada., Kamath B; Division of Gastroenterology, Hepatology and Nutrition, Sick Kids Hospital, Toronto, Ontario, Canada., Aleman TS; Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Jazyk:	angličtina
Zdroj:	Ophthalmic genetics [Ophthalmic Genet] 2024 Oct; Vol. 45 (5), pp. 522-531. Date of Electronic Publication: 2024 Jul 02.
DOI:	10.1080/13816810.2024.2362214
Abstrakt:	Purpose: To explore patterns of disease expression in Alagille syndrome (ALGS). Methods: 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. Results: 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. Conclusion: 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.
Databáze:	MEDLINE
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