Novel Forkhead Box C1 Gene Mutation with Significant Postnatal Iris Growth and Modulation in a Child with Anterior Segment Dysgenesis

摘要

Purpose : The term anterior segment dysgenesis describes a complex of disorders consisting of corneal, lens or whole eye abnormalities, which may result in detrimental visual consequences. The most commonly mutated genes are PITX2, FOXC1 and PAX6. The natural history is one of progressive decline of visual function due to development of a corneal pannus or opacities, corneal perforation, refractory glaucoma, progressive iris atrophy or phthisis. We are reporting the ocular and genetic findings of a patient with Axenfeld-Rieger syndrome with a novel FOXC1 mutation and major postnatal iris growth and partial normalization of anatomy in the absence of surgical intervention. Methods : Longitudinal observation of the proband was performed from age 3 months to 5 years with repeat comprehensive ophthalmologic examinations, including visual acuity, slit lamp examination, gonioscopy, and dilated fundus examination. Genomic DNA from the patient with Axenfeld-Rieger syndrome and from his parents was amplified by polymerase chain reaction and subjected to direct DNA sequencing. Results : A novel FOXC1 mutation, c.314_316delACCinsCCT, was identified in this patient with Axenfeld-Rieger syndrome. This mutation causes a loss of normal protein function through protein truncation. The patient also exhibited regenerative iris changes with posterior embryotoxon and glaucoma in one eye and aniridia in the fellow eye. Conclusions : The observed postnatal iris growth is significant, since it constitutes the first known report of hyperplastic changes in ARS; previous literature has described the iris changes in Axenfeld-Rieger as atrophic. Several observers have theorized that contraction of an abnormal membrane on the anterior surface of the iris composed of collagen and ground substance, demonstrated on histopathologic study, causes the corectopia, ectropion uveae, and iris atrophy as seen in ARS. The exact mechanism of this patienta??s postnatal iris growth remains unclear; however, changes quite similar to those seen in our patient have been reported in human FOXC1 mutations classified as hypermorphic.This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.??View OriginalDownload Slide.