Razek Georges Coussa1,2,3, Yue Zhao1, Meghan J DeBenedictis1, Allison Babiuch1, Jonathan Sears1,3, Elias I Traboulsi1,3. 1. Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. 2. Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA. 3. Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, Ohio, USA.
Abstract
Purpose: Neonatal retinal folds and/or vitreoretinal traction can be signs of isolated ocular or syndromic disorders. Etiologies include retinopathy of prematurity, perinatal infections or inherited vitreoretinal disorders such as familial exudative vitreoretinopathy (FEVR) or Norrie disease. We present the clinical and genetic findings of a two-month-old infant with microcephaly, mild motor developmental delay, and FEVR, who required urgent surgical interventions. Methods: The patient underwent an initial examination under anesthesia (EUA) with fluorescein angiography (FA) and subsequent medical and surgical treatments. Genetic testing was undertaken to identify the etiology. Results: Examination at 2 months of age demonstrated microcephaly with a head circumference smaller than the 1st percentile. Family history was negative for microcephaly or retinal disease. Anterior segment eye exam was normal OU. There were bilateral macular folds involving the fovea and extending from the disc to the temporal periphery. FA demonstrated bilateral incomplete vascularization of the retina most notable nasally. Indirect laser was applied to ischemic retina OU. Scleral buckling procedures were performed OU as well as a vitrectomy in the left eye. Follow-up examinations demonstrated the stable appearance of the folds and attached retinas OU. Genetic testing identified a novel dominant heterozygous c.2046_2047del [p.Phe683Glnfs*9] mutation in CTNNB1, predicted to result in a frameshift causing a truncated protein.Conclusions: CTNNB1 mutations are an uncommon cause of FEVR with microcephaly.
Purpose: Neonatal retinal folds and/or vitreoretinal traction can be signs of isolated ocular or syndromic disorders. Etiologies include retinopathy of prematurity, perinatal infections or inherited vitreoretinal disorders such as familial exudative vitreoretinopathy (FEVR) or Norrie disease. We present the clinical and genetic findings of a two-month-old infant with microcephaly, mild motor developmental delay, and FEVR, who required urgent surgical interventions. Methods: The patient underwent an initial examination under anesthesia (EUA) with fluorescein angiography (FA) and subsequent medical and surgical treatments. Genetic testing was undertaken to identify the etiology. Results: Examination at 2 months of age demonstrated microcephaly with a head circumference smaller than the 1st percentile. Family history was negative for microcephaly or retinal disease. Anterior segment eye exam was normal OU. There were bilateral macular folds involving the fovea and extending from the disc to the temporal periphery. FA demonstrated bilateral incomplete vascularization of the retina most notable nasally. Indirect laser was applied to ischemic retina OU. Scleral buckling procedures were performed OU as well as a vitrectomy in the left eye. Follow-up examinations demonstrated the stable appearance of the folds and attached retinas OU. Genetic testing identified a novel dominant heterozygous c.2046_2047del [p.Phe683Glnfs*9] mutation in CTNNB1, predicted to result in a frameshift causing a truncated protein.Conclusions: CTNNB1 mutations are an uncommon cause of FEVR with microcephaly.
Authors: Linda Z Rossetti; Mir Reza Bekheirnia; Andrea M Lewis; Heather C Mefford; Katie Golden-Grant; Kristina Tarczy-Hornoch; Lauren C Briere; David A Sweetser; Melissa A Walker; Elijah Kravets; David A Stevenson; Georgette Bruenner; Jessica Sebastian; Julia Knapo; Jill A Rosenfeld; Paul C Marcogliese; Michael F Wangler Journal: Mol Genet Genomic Med Date: 2020-12-22 Impact factor: 2.183