FZD4 – Persistent Hyperplastic Primary Vitreous

Familial exudative vitreoretinopathy (FEVR)–associated gene FZD4 encodes the Wnt receptor frizzled-4, critical for retinal vascular development. Persistent hyperplastic primary vitreous (PFV) is defined by failed regression of the hyaloid vasculature and may phenocopy FEVR. A 4-month-old infant presented with unilateral retrolental membrane and near-complete retinal detachment initially diagnosed as PFV, but wide-field fluorescein angiography revealed bilateral avascular retina and vascular leakage, prompting genetic testing that identified a heterozygous FZD4 mutation and revised the diagnosis to FEVR (PMID:28413837). Although only a single case links FZD4 variants to PFV presentation, functional assays in Xenopus laevis embryos show that FZD4 mutations disrupt Wnt/Ca2+ signaling and retinal angiogenesis, providing mechanistic support for persistent vascular defects (PMID:12172548). This limited evidence suggests FZD4 testing should be considered in atypical PFV cases to refine diagnosis and guide early treatment.

References

• American journal of ophthalmology case reports • 2017 • Familial exudative vitreoretinopathy presentation as persistent fetal vasculature. PMID:28413837
• Nature genetics • 2002 • Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy. PMID:12172548

Evidence Based Scoring (AI generated)