Retinal Features of Family Members With Familial Exudative Vitreoretinopathy Caused By Mutations in KIF11 Gene

PURPOSE: To determine the clinical characteristics of patients and family members with familial exudative vitreoretinopathy (FEVR) caused by mutations in the KIF11 gene. METHODS: Twenty-one patients from 10 FEVR families with mutations in the KIF11 gene were studied. The retinal and systemic features were examined. The genetic analyses performed included Sanger sequencing of the KIF11 gene, whole exome sequencing, as well as array comparative genomic hybridization (CGH) analysis and multiple ligation probe assay (MLPA). RESULTS: Sequence analysis revealed seven different KIF11 mutations. Array CGH with MLPA revealed two different exon deletions. All probands had advanced FEVR with retinal detachments (RDs) and microcephaly with or without developmental disabilities. Patients with bilateral RDs were more frequently associated with developmental disabilities (P = 0.023). Multimodal imaging of the family members revealed that six of nine patients without RDs (66%) had varying degrees of chorioretinopathy. The retinal folds in FEVR patients were associated with severe retinal avascularization. However, funduscopic changes in the peripheral retina were unremarkable in family members without RDs. A score representing the peripheral vascular anomalies determined from the fluorescein angiograms was lower than that of control eyes of patients with mutations of the Wnt signaling genes (P = 0.0029). CONCLUSIONS: The probands with KIF11 mutations were associated with severe ocular and systemic pathologies, whereas affected family members showed highly variable clinical manifestations. Peripheral vascular anomalies can often be unremarkable in eyes without RDs. TRANSLATIONAL RELEVANCE: These findings highlight more diverse mechanisms that underlie the pathological changes in patients with FEVR.