Retinal findings and a novel TINF2 mutation in Revesz syndrome: Clinical and molecular correlations with pediatric retinal vasculopathies

• Published in: Ophthalmic genetics 2017-01, Vol.38 (1), p.51-60
• Main Authors: Gupta, Mrinali P, Talcott, Katherine E, Kim, David Y, Agarwal, Suneet, Mukai, Shizuo
• Format: Article
• Language: English
• Subjects: Bone Diseases, Metabolic - diagnosis; Bone Diseases, Metabolic - genetics; Bone Marrow - abnormalities; Brain - abnormalities; Diseases in Twins - genetics; Female; Fluorescein Angiography; Gestational Age; Humans; Infant; Magnetic Resonance Imaging; Mutation; Photography; Polymerase Chain Reaction; Retina; Retinal Diseases - diagnosis; Retinal Diseases - genetics; Retinal Vessels - pathology; Telomere-Binding Proteins - genetics; Twins, Monozygotic - genetics
• ISSN: 1381-6810; 1744-5094
• DOI: 10.1080/13816810.2016.1275019

Revesz syndrome is a telomere disorder in the dyskeratosis congenita (DKC) spectrum characterized by exudative retinopathy, bone marrow failure, neuroradiographic abnormalities, and integumentary findings. We report the ophthalmologic findings, documented by examinations under anesthesia with clinical photography and fluorescein angiography, as well as the systemic manifestations and genetic and molecular testing, in identical twins with Revesz syndrome, and compare and contrast these features to those of other pediatric retinal vasculopathies. Both twins exhibited widespread avascularity and anomalous vasculature of the retinal periphery, retinal telangiectasias, and exudation. One twin developed a combination exudative/tractional/rhegmatogenous retinal detachment, while the other exhibited a focal collection of buds of retinal neovascularization. Both twins developed bone marrow failure and were found to have cerebellar hypoplasia and widespread cerebral calcifications. Telomere testing in lymphocytes and granulocytes revealed telomere length less than the 1st percentile for age, and gene sequencing revealed a novel mutation in the TINF2 gene, resulting in the T284P TIN2 protein variant. We report ophthalmic findings in twins with Revesz syndrome due to a previously unreported mutation in TINF2 and propose that phenotypic and molecular overlaps between DKC spectrum disorders and pediatric retinal vasculopathies may reflect a shared pathophysiologic basis.