Clinical and genetic heterogeneity in multifocal vitelliforin dystrophy

Objective: To describe the clinical and genetic findings in 15 patients with multifocal vitelliform lesions. Methods: All patients and, if possible, affected family members underwent an ophthalmic examination and their genomic DNA was analyzed for mutations in the vitelliform macular dystrophy 2 (VMD2) gene. Patients who did not have a mutation in the VMD2 gene were screened for mutations in the peripherin/RDS gene. Results: Patient age at onset of the disease was highly variable, ranging from 5 to 59 years. The peripheral lesions varied in number, size, and overall appearance but showed similar characteristics at autofluorescence imaging and optical coherence tomography compared with the central vitelliform lesion. Mutations in the VMD2 gene were identified in 9 of 15 patients. One patient without a VMD2 mutation carried a sequence variant in the 5' untranslated region of the peripherin/RDS gene. Conclusions: Multifocal vitelliform dystrophy is a clinically and genetically heterogeneous retinal disease that can be caused by mutations in the VMD2 gene. Other genes associated with this phenotype remain to be identified. Clinical Relevance: Clinical and molecular genetic characterization of multifocal vitelliform dystrophy may lead to better understanding of the pathophysiological mechanisms underlying this phenotype and may enable a more accurate prognosis in individual patients.