Cone-rod dystrophy can be a manifestation of Danon disease

Abstract

BackgroundDanon disease is a neuromuscular disorder with variable expression in the eye. We describe a family with Danon disease and cone-rod dystrophy (CRD).MethodsAffected 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.ResultsTwo 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 fields demonstrated central scotoma. The causal mutation was p.Gly384Arg in LAMP2; no mutations were found in RPGR.ConclusionsThis 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.

Danon disease – dysregulation of autophagy in a multisystem disorder with cardiomyopathy

“…Specifically, ventricular (Hedberg Oldfors et al, 2015;Miani et al, 2012;Maron et al, 2009;Lobrinus et al, 2005) and atrial (Charron et al, 2004) arrhythmias have both been reported and are often severe, even in women (Miani et al, 2012). Additionally, individuals with Danon disease can also develop (usually relatively mild) skeletal myopathy (80-90% of males), primarily mild cognitive defects and learning disabilities (70-100% of males), and visual problems (69% of males) (Thiadens et al, 2012;Schorderet et al, 2007;Prall et al, 2006;D'souza et al, 2014). For a complete and recent review of clinical descriptions of affected individuals, see D'souza et al (2014).…”

“…Clearly, further investigation is needed to better understand the pathological phenotype in the brain. Some clinical studies have described the ophthalmic manifestations of individuals with Danon disease (Thiadens et al, 2012;Prall et al, 2006;Lobrinus et al, 2005). Both male individuals with Danon disease and female carriers have been found to have retinopathy, including peripheral pigmentary retinopathy (Prall et al, 2006) and peripheral 'salt-and-pepper' retinopathy (Schorderet et al, 2007;Thiadens et al, 2012), although sometimes the condition is milder in females.…”

“…Some clinical studies have described the ophthalmic manifestations of individuals with Danon disease (Thiadens et al, 2012;Prall et al, 2006;Lobrinus et al, 2005). Both male individuals with Danon disease and female carriers have been found to have retinopathy, including peripheral pigmentary retinopathy (Prall et al, 2006) and peripheral 'salt-and-pepper' retinopathy (Schorderet et al, 2007;Thiadens et al, 2012), although sometimes the condition is milder in females. In one study, both enrolled males had a near-complete loss of pigmentation of the retinal pigment epithelium (RPE) in the macula (Prall et al, 2006), whereas a boy from another study had RPE hypopigmentation (Schorderet et al, 2007).…”

“…In one study, both enrolled males had a near-complete loss of pigmentation of the retinal pigment epithelium (RPE) in the macula (Prall et al, 2006), whereas a boy from another study had RPE hypopigmentation (Schorderet et al, 2007). Another study of a family found that two out of four male members with Danon disease developed cone-rod dystrophy, with thinning of the RPE and overlying photoreceptor layers (Thiadens et al, 2012). Photoreceptor cells (comprised of rods and cones) absorb photons of light through components called photoreceptor outer segments (POSs).…”

Cone-rod dystrophy in Danon disease

“…In this issue, Thiadens and colleagues report ophthalmoscopic findings of macular disruption and physiologic findings of cone-rod dystrophy in two of four cousins from a family with Danon disease, a rare X-linked disorder characterized by muscle weakness, cardiomyopathy, and mental impairment, which has been mapped to mutations in the lysosomeassociated membrane protein gene, LAMP2 (OMIM #300257) [1].…”