Background Danon disease is a neuromuscular disorder with variable expression in the eye. We describe a family with Danon disease and cone-rod dystrophy (CRD). Methods Affected males of one family with Danon were invited for an extensive ophthalmologic examination, including color vision testing, fundus photography, Goldmann perimetry, full-field electroretinogram (ERG), and SD-OCT. Previous ophthalmologic data were retrieved from medical charts. The LAMP2 and RPGR gene were analyzed by direct sequencing. Results Two siblings had no ocular phenotype. The third sibling and a cousin developed CRD leading to legal blindness. Visual acuity deteriorated progressively over time, color vision was severely disturbed, and ERG showed reduced photopic and scotopic responses. SD-OCT revealed thinning of the photoreceptor and RPE layer. Visual fieldsdemonstrated central scotoma. The causal mutation was p. Gly384Arg in LAMP2; no mutations were found in RPGR. Conclusions This is the first description of CRD in Danon disease. The retinal phenotype was a late onset but severe dystrophy characterized by loss of photoreceptors and RPE cells. With this report, we highlight the importance of a comprehensive ophthalmologic examination in the clinical work-up of Danon disease.

Cone-rod dystrophy . LAMP2 gene . Genotype-phenotype correlations . RPE pathology. Danon disease,
Graefe's Archive for Clinical and Experimental Ophthalmology
Department of Ophthalmology

Thiadens, A.A.H.J, Slingerland, N.W.R, Florijn, R.J, Visser, G.H, Riemslag, F.C.C, & Klaver, C.C.W. (2012). Cone-rod dystrophy can be a manifestation of Danon disease. Graefe's Archive for Clinical and Experimental Ophthalmology, 250(5), 769–774. doi:10.1007/s00417-011-1857-8