Occult Macular Dystrophy (Miyake’s Disease)

Abstract

Occult macular dystrophy (OMD; OMIM 613587), first described by Miyake et al. in 1989, is an inherited macular dystrophy characterized by a progressive decrease in the visual acuity in eyes with a normal appearing fundus and normal fluorescein angiograms (Miyake Y, Ichikawa K, Shiose Y, Kawase Y, Am J Ophthalmol,108:292–9, 1989). The full-field electroretinograms (ERGs) are usually normal; however the focal macular ERGs, multifocal ERGs, and pattern ERGs are abnormal. Heterozygous mutations in the retinitis pigmentosa 1-like 1 (RP1L1) gene (OMIM 608581) cause this ocular condition, (Akahori M, Tsunoda K, Miyake Y, et al, Am J Hum Genet, 87:424–9, 2010, Tsunoda K, Usui T, Hatase T, et al, Retina J Retinal Vitreous Dis 32:1135–47, 2012, Miyake Y, Tsunoda K, Jpn J Ophthalmol, 59:71–80, 2015) and OMD with the RP1L1 mutations has been specifically designated as Miyake’s disease (Fujinami K, Kameya S, Kikuchi S, et al, Invest Ophthalmol Vis Sci, 57:4837–46, 2016). Characteristic changes in the microstructure of the photoreceptors have been detected by spectral-domain optical coherence tomography (SD-OCT) in eyes with Miyake’s disease (Tsunoda K, Usui T, Hatase T, et al, Retina J Retinal Vitreous Dis 32:1135–47, 2012, Fujinami K, Kameya S, Kikuchi S, et al, Invest Ophthalmol Vis Sci, 57:4837–46, 2016). The most common mutation is the c.133C > T, p.Arg45Trp mutation in exon 2, and there is another hot spot between amino acid numbers 1194 and 1201 in exon 4 which is downstream of the doublecortin domain (Fujinami K, Kameya S, Kikuchi S, et al, Invest Ophthalmol Vis Sci, 57:4837–46, 2016, Kabuto T, Takahashi H, Goto-Fukuura Y, et al, Mol Vis, 18:1031–9, 2012, Davidson AE, Sergouniotis PI, Mackay DS, et al, Hum Mutat, 34:506–14, 2013). In addition to the typical phenotype of OMD, extensive retinal dysfunction such as generalized cone dysfunction and generalized rod-cone dysfunction has been documented in patients with biallelic mutations in the RP1L1 gene (Davidson AE, Sergouniotis PI, Mackay DS, et al, Hum Mutat, 34:506–14, 2013, Kikuchi S, Kameya S, Gocho K, et al, Biomed Res Int, 2015:545243, 2015).