This 41YO female complained of increasing difficulties with dark adaptation and night vision. Vision was 20/25 OU.
Color imaging shows bilateral, multifocal, partially scrambled vitelliform lesions. The superior scrambled aspect of each lesion on OCT shows subretinal hyporeflectivity, and the inferiorly layered vitelliform material is hyperreflective. The inferior vitelliform material is markedly hyper-autofluorescent with Optos imaging.
Genetic testing was positive for a heterozygous pathogenic IMPG1 deletion in exon 7.
Interestingly, her brother was recently diagnosed with Best disease, having more typical single, subfoveal yellow vitelliform lesions. The brother’s genetic testing showed a similar IMPG1 mutation.
Learning Points:
Best disease is most often associated with a mutation in the BEST1 gene, which encodes bestrophin-1. Bestrophin-1, a calcium-activated chloride channel, is primarily found in the basolateral plasma membrane of the RPE.
BEST1 mutations cause a variety of phenotypes, including autosomal recessive bestrophinopathy, best vitelliform macular dystrophy, and autosomal dominant vitreoretinochoroidopathy.
Multifocal lesions are a rare phenotype and are not usually associated with subfoveal lesions. Multifocal Best needs to be differentiated from other causes of multifocal serous detachments, including multifocal central serous, autosomal recessive bestrophinopathy (see Boon et al, Ophthalmology 2013;120:809-820), and idiopathic or paraneoplastic acute exudative polymorphous vitelliform maculopathy (see Barbazetto et al, Ophthalmology 2018;125:75-88).
Vitelliform macular dystrophies (VMD) are most commonly caused by BEST1, PRPH2, or VMD2 mutations. IMPG1 and IMPG2, which encode proteins that are components of the interphotoreceptor matrix, have also been implicated in both autosomal dominant and recessive VMD.
Manes et al. reported a wide variety of IMPG1 VMD phenotypes, including multifocal lesions and more classic single subfoveal lesions, as seen in our two patients (Am J Hum Genet 2013;93:571-578).
