Xp11.3 microdeletion causing Norrie disease and X-linked Kabuki syndrome

PURPOSE: To describe a novel case of Norrie disease and X-linked Kabuki syndrome caused by a microdeletion encompassing multiple genes on the X chromosome. OBSERVATIONS: A 3-day-old boy born at full term had bilateral retrolental fibrovascular plaques. Surgery with lensectomy and vitrectomy revealed bilateral, closed funnel retinal detachments consistent with a clinical diagnosis of Norrie disease. In addition, the baby had congenital heart defects, hearing loss, and dysmorphic facies. His mother carried a clinical diagnosis of Kabuki syndrome. Genetic testing of the baby revealed an Xp11.3 microdeletion that included the NDP and KDM6A genes, confirming the baby had both Norrie disease and X-linked Kabuki syndrome. The mother was found via ultrawide-field fluorescein angiography to have asymptomatic peripheral retinal vascular anomalies, consistent with NDP-associated familial exudative vitreoretinopathy (FEVR). CONCLUSIONS AND IMPORTANCE: This is the first reported case of Norrie disease together with X-linked Kabuki syndrome. Contiguous gene deletions may explain some of the variable systemic involvement in Norrie disease.