Familial exudative vitreoretinopathy (FEVR) is a rare genetic disorder of retinal vascular development that can result in retinal detachment and blindness. 1 A pathologic hallmark of FEVR is peripheral retinal avascularity, which promotes ischemia, neovascularization, and ultimately vitreoretinal traction and detachment of the retina in severe cases. Mutations in five genes 2–7 have been associated with the FEVR phenotype, and many of these genes play an essential role in Wnt signaling. Wnts are glycoproteins that bind to specific transmembrane receptors to initiate intracellular signaling cascades, 8, 9 and normal Wnt signaling within developing retinal endothelial cells is crucial to the formation of a well-vascularized retina. We report a patient with a heterozygous mutation in the CTNNB1 gene, which codes for the protein beta-catenin. Beta-catenin is the final mediator of gene transcription in canonical Wnt signaling. 10 To the best of our knowledge, this is the first report of a CTNNB1 mutation that has been linked to the FEVR phenotype. A 22-month-old boy was referred to the WK Kellogg Eye Center for evaluation of “depth perception problems.” The patient’s past medical history included lipomyelomeningocele, failure to thrive, short stature, developmental delay, and behaviors on the autism spectrum. The patient was born at 34 and 1/7 week gestation with a birth weight of 1842 g. Newborn screening was normal. The patient had previously been evaluated by Pediatric Genetics and a heterozygous mutation in the CTNNB1 gene was identified by clinical whole exome sequencing (GeneDx, Gaithersburg, MD). The mutation was characterized as an insertion of five base pairs (c. 2112_2116dupAGAAC; p. P706QfsX31), causing a frameshift of the protein and likely complete loss-of-function, resulting in haploinsufficiency. The mutation was not found in the mother, who was the only parent available for testing. Based on the type of mutation and the patient’s clinical features, it was presumed to be causative of his developmental delay and congenital anomalies. At his initial visit to the eye center at age 22 months, the patient’s exam was notable for bilateral hyperopic astigmatism. Spectacles were prescribed and the patient was to follow-up in 6 months, but he was lost to followup for over 14 months. On return visit, he was noted to have a left eye preference and dilated examination revealed an abnormality in the right eye concerning a retinal detachment. Examination under anesthesia showed normal anterior segments of both eyes. Fundoscopic examination of the right eye revealed an exudative macular detachment with retinal elevation in the peripapillary area extending to the inferotemporal periphery (Figure 1A). Also present were the initial stages of retinal fold formation in the posterior pole with a falciform fold in the inferotemporal periphery. Vitreous overlying this fold was abnormal and generating traction, and exudates were present at the base of the fold. The retinal periphery was markedly avascular. Fundoscopic examination of the left eye revealed an elevated optic nerve, a normal macula, and premature pruning of the temporal retinal vessels (Figure 1C). Fluorescein angiography revealed early leakage from the abnormal retinal vessels (Figure 1B). The peripheral vessels were pruned off with complete avascularity of the far periphery. The left eye showed similar peripheral vascular pruning temporally more than nasally (Figure 1D). The findings on EUA were consistent with the FEVR phenotype. To prevent disease progression, the patient underwent laser photocoagulation of the peripheral retina of the right eye during the initial EUA. He subsequently …