Genotypic Distribution and Clinical Correlations in Familial Exudative Vitreoretinopathy: A Single-Center Study.

Purpose: To report the role of wide-angle imaging in detecting suspicious cases of familial exudative vitreoretinopathy (FEVR) in pediatric patients with unexplained vision loss and describe genotypic distribution and examples of phenotypes.

Design: A retrospective cohort study was conducted at a single tertiary referral center in the Intermountain West.

Subjects And Participants: Patients diagnosed with FEVR or atypical retinopathy of prematurity (ROP) between 2010 and 2021 at the University of Utah. Twenty-five families with FEVR were included, with 21 families undergoing genetic testing. Eight families with atypical ROP were included.

Methods: We conducted a retrospective analysis of patients referred with unexplained vision loss and diagnosed with FEVR at the pediatric retina center at the University of Utah from 2010 to 2021. Clinical examination and wide-angle fluorescein angiography (FA) were performed. Patients identified with abnormal peripheral retinal or intravitreal vascularization were recommended for genetic testing. Next-generation sequencing was used to identify variants in known genes associated with FEVR. The positivity rate and the proportion of each positive genetic mutation were calculated. We also include a small cohort of premature infants with atypical ROP who underwent genetic testing prior to the examination under anesthesia.

Main Outcome Measures: Detection rate of FEVR-associated mutations.

Results: Genetic variants were identified in 85.7% of families who underwent testing, exceeding previously reported detection rates. LRP5 (33.3%) and FZD4 (19%) were the most common mutations. Indeterminate results were reported in 4.8% of cases, while 9.5% had negative results for FEVR-associated mutations. Among the 8 premature infants with atypical regression of ROP, none tested positive for FEVR-associated genotypes. We described 5 illustrative cases that demonstrate unique presentations in our cohort, including those showing phenotypic variability or masquerading as other disorders.

Conclusions: The findings highlight the genotypic and phenotypic heterogeneity of FEVR and underscore the value of wide-angle FA to trigger obtaining genetic testing for accurate diagnosis. A high clinical suspicion for FEVR is recommended in pediatric patients with unexplained vision loss and vitreoretinal abnormalities. Future studies are needed to investigate additional genetic modifiers and refine genotype-phenotype correlations.

Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.