A novel variant in the FZD4 gene leading to familial exudative vitreoretinopathy: A case report and literature review

Abstract

Rationale: Familial exudative vitreoretinopathy (FEVR) is a genetically heterogeneous retinal vascular disorder. This report describes a novel frizzled class receptor 4 (FZD4) gene mutation (c.977C>T) identified in a FEVR pedigree and highlights its phenotypic variability and clinical management.

Patient concerns: A neonatal proband was referred for routine RetCam III fundus screening on postnatal day 3. No systemic abnormalities were reported, but retinal abnormalities were detected.

Diagnoses: Fundus examination revealed asymmetric retinopathy, with a white temporal demarcation line in the right eye and extensive avascular zones with exudative proliferation in the left. Genetic testing confirmed a heterozygous FZD4 mutation (c.977C>T) in the proband and affected family members, consistent with autosomal dominant FEVR.

Interventions: The proband received prophylactic retinal photocoagulation in both eyes and underwent regular ophthalmic follow-up. Family members with mild retinal changes were monitored.

Outcomes: At 12 months of age, the proband achieved normal visual acuity with stable retinal status. Adult carriers exhibited only mild peripheral vascular anomalies, suggesting incomplete penetrance and variable expressivity.

Lessons: This case expands the mutation spectrum of FZD4 and underscores the importance of neonatal fundus screening and genetic analysis for early detection of FEVR. Prompt intervention can preserve visual function despite underlying genetic heterogeneity.

Keywords: case report; familial exudative vitreoretinopathy; genetic etiology; whole-exome sequencing.