Clinical and Genetic Features of Familial Exudative Vitreoretinopathy With Only-Unilateral Abnormalities in a Chinese Cohort

Abstract

Importance: Familial exudative vitreoretinopathy (FEVR) with only-unilateral abnormalities may masquerade as other vitreoretinal disorders. Clinicians should be vigilant of patients with unilateral FEVR, recognizing that the relatively normal vision of the fellow eye could compromise a patient's attention to the decreasing vision of the affected eye.

Objective: To describe the clinical findings and genetic spectrum of patients with FEVR and only-unilateral abnormalities.

Design, setting, and participants: A medical records review included all patients (N = 621) with a diagnosis of FEVR between January 1, 2010, and October 31, 2017, from Xinhua Hospital in Shanghai, China. Patients were excluded if retinal abnormalities were noted in both eyes or if a diagnosis of FEVR could not be confirmed by genetic testing. Inclusion criteria included clinical diagnosis of FEVR with only-unilateral features on widefield angiography and confirmed mutations in 5 FEVR targeted genes (LRP5, FZD4, ZNF408, NDP, and TSPAN12).

Exposures: Clinical data were collected from patient medical records. Widefield angiography and targeted gene sequencing were performed in all patients of this cohort.

Main outcomes and measures: Clinical findings and genetic spectrum.

Results: Of the 621 patients with a clinical diagnosis of FEVR, 20 with unilateral FEVR (3.22%; 95% CI, 1.83%-4.61%; 18 males [90%] and a mean [SD] age at presentation of 2.6 [2.7] years) were identified. All patients were Han Chinese. The most common clinical presentations were total retinal detachment (12 [60%]) and retinal fold (6 [30%]). Mutations in the LRP5 gene were the most prevalent (11 [55%]), followed by the genes FZD4 (4 [20%]), ZNF408 (2 [10%]), TSPAN12 (2 [10%]), and NDP (1 [5%]).

Conclusions and relevance: The findings of this study suggest that the identification of unilateral peripheral retinal abnormalities should include a consideration of FEVR, perhaps more often seen with mutations in the LRP5 gene; variable phenotypic penetrance of the retinal abnormalities can lead to seemingly unilateral disease.

Figure 1.. Color and Fluorescein Angiography of Patient 9 With Coats Disease–Like Presentation Secondary to Familial Exudative Vitreoretinopathy

Figure 2.. Genetic Spectrum in Patients With the Bilateral or the Only-Unilateral Familial Exudative Vitreoretinopathy (FEVR)

Among 20 patients with unilateral FEVR, LRP5 was the most frequently mutated gene in 11 (55%) patients, followed by genes FZD4 (4 [20%]), ZNF408 (2 [10%]), TSPAN12 (2 [10%]), and NDP (1 [5%]). Among 284 patients with bilateral FEVR, the most frequently mutated gene was LRP5 (93 [33%]), followed by genes FZD4 (71 [25%]), KIF11 (44 [15.5%]), TSPAN12 (37 [13%]), NDP (26 [9%]), and ZNF408 (13 [4.5%]).