Robert M Carroll1, Benjamin J Kim1. 1. Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Abstract
Background: Familial exudative vitreoretinopathy (FEVR) is a disorder of retinal angiogenesis associated with mutations in multiple genes related to the Wnt pathway. The disease is characterized by a spectrum of ophthalmic manifestations that range from asymptomatic to blinding. While FEVR has classically been considered a diagnosis made in the pediatric population, it can be seen in adults and lead to vision loss if unidentified. We present three asymptomatic adults in a single, five-member family with clinical findings and genetic testing supportive of a diagnosis of FEVR.Materials and Methods: Case series. All patients underwent ophthalmologic examination, diagnostic imaging, and genetic testing. Results: A 32-year-old female was referred for evaluation of abnormal retinal vessels. Clinical examination and diagnostic testing revealed retinal vascular dragging, peripheral avascularity, and retinal neovascularization suggestive of a diagnosis of FEVR. Genetic testing was positive for a heterozygous intronic variant (c.149 + 3A>G) in TSPAN12. The same variant was identified in the patient's mother and one adult sister, each showing evidence of early stage FEVR. The patient's father and second adult sister had normal eye exams with negative genetic testing. All patients were asymptomatic with good vision.Conclusions: FEVR can be first diagnosed in asymptomatic adult patients who may require treatment. The disease, therefore, may be incompletely characterized and under diagnosed. The specific variant in TSPAN12 identified in this family may be associated with early stage FEVR or disease that manifests later in life. Clinical correlation with exact variants such as this may enhance our understanding of this disease.
Background: Familial exudative vitreoretinopathy (FEVR) is a disorder of retinal angiogenesis associated with mutations in multiple genes related to the Wnt pathway. The disease is characterized by a spectrum of ophthalmic manifestations that range from asymptomatic to blinding. While FEVR has classically been considered a diagnosis made in the pediatric population, it can be seen in adults and lead to vision loss if unidentified. We present three asymptomatic adults in a single, five-member family with clinical findings and genetic testing supportive of a diagnosis of FEVR.Materials and Methods: Case series. All patients underwent ophthalmologic examination, diagnostic imaging, and genetic testing. Results: A 32-year-old female was referred for evaluation of abnormal retinal vessels. Clinical examination and diagnostic testing revealed retinal vascular dragging, peripheral avascularity, and retinal neovascularization suggestive of a diagnosis of FEVR. Genetic testing was positive for a heterozygous intronic variant (c.149 + 3A>G) in TSPAN12. The same variant was identified in the patient's mother and one adult sister, each showing evidence of early stage FEVR. The patient's father and second adult sister had normal eye exams with negative genetic testing. All patients were asymptomatic with good vision.Conclusions: FEVR can be first diagnosed in asymptomatic adult patients who may require treatment. The disease, therefore, may be incompletely characterized and under diagnosed. The specific variant in TSPAN12 identified in this family may be associated with early stage FEVR or disease that manifests later in life. Clinical correlation with exact variants such as this may enhance our understanding of this disease.