Aims To explore the clinical and genetical features of families with strictly confirmed familial exudative vitreoretinopathy (FEVR) in a large Chinese cohort.

Methods A retrospective chart review study was conducted on the FEVR families diagnosed by both angiography and targeted next-generation sequencing in six FEVR known genes (FZD4, LRP5, TSPAN12, NDP, KIF11, ZNF408) in the probands and at least one first-degree family member. Variation in expressivity and severity was evaluated in different gene groups.

Results 105 FEVR families (223 FEVR affected subjects with 434 eyes) met the inclusion criteria. There were 105 probands with mean age of 3.8 years old and 118 affected family members of 32.7 years old averagely. Mutations in FZD4 were most prevalent (33.33%), followed by LRP5 (29.52%), TSPAN12 (22.86%), NDP (5.71%), KIF11 (1.9%) and ZNF408 (0.95%). 81% of the probands were classified as stage 4 or worse which most prevalently contributed to FZD4 mutations. All of the three affected family members with stage 4 or worse carried FZD4 variants. More than half (51.43%) of the probands in FZD4 group showed asymmetry. Unilateral FEVR was detected in 11 (10.5%) families consisting of six probands and six affected relatives, and FZD4 mutations accounted for 63.64% of all the cases with variant (c.1282_1285del, p. D428fs) identified in three families.

Conclusions Genotype-phenotype correlation in FEVR was complex with family dependent. Mutations in FZD4 might initiate the most diverse and asymmetric phenotypes.