Ophthalmic Manifestations of Danon Disease F. Ryan Prall, MD, 1 Arlene Drack, MD, 1 Matthew Taylor, MD, PhD, 2 Lisa Ku, MS, 2 Jeffrey L. Olson, MD, 1 Darren Gregory, MD, 1 Luisa Mestroni, MD, 2 Naresh Mandava, MD 1 Purpose: To describe the ophthalmic findings in patients with Danon disease, an X-linked condition causing cardiomyopathy in males and females. Design: Retrospective case series. Participants: Patients with genetically proven Danon disease. Methods: Retrospective chart review of complete eye examinations including electroretinogram, visual fields, and fluorescein angiography. Results: Five females (4 affected) and 2 affected males were examined. The 4 affected females demonstrated a peripheral pigmentary retinopathy. Lens changes, myopia, abnormal electroretinogram and visual fields were also found. The males demonstrated a near-complete loss of pigment in the retinal pigment epithelium. Conclusion: We report the first description of a characteristic retinopathy in patients with Danon disease and the first extracardiac manifestations in affected females. Retinopathy potentially could be used to identify asymptomatic carriers. Ophthalmology 2006;113:1010 –1013 © 2006 by the American Academy of Ophthalmol- ogy. Danon disease is an X-linked cardioskeletal myopathy first described by Danon et al in 1981 in a report of 2 boys with cardiomyopathy, myopathy, and mental retardation. 1 It is caused by a mutation in the lysosome-associated membrane protein-2 (LAMP-2) gene, which leads to a deficiency of a major lysosomal membrane protein, and is characterized pathologically by intracytoplasmic vacuoles containing au- tophagic material and glycogen in skeletal and cardiac mus- cle cells. 1–4 The clinical triad of cardiomyopathy, myopathy, and variable mental retardation in males has been substanti- ated by several reports and most notably by Sugie et al, 5 who reported their findings in 38 patients with Danon disease. Female mutation carriers show a milder pheno- type, which has to date been essentially restricted to cardiac disease. Cardiac disease in males includes Wolff– Parkinson–White (WPW) syndrome and cardiomyopathy that is typically hypertrophic, although dilated forms have been described. Females are more likely to manifest only WPW, but both dilated and hypertrophic cardiomy- opathies and skeletal myopathies may be encountered. 5 Cardiac complications in males are often severe; many patients require permanent pacemakers and heart trans- plantation. Myopathy is typically mild and may be asymptomatic. Often it is only evidenced by an increase in serum creatine kinase levels and abnormalities in electromyography. When symptomatic, patients present with proximal limb muscle weakness that is slowly pro- gressive. Mental retardation in the mild range affects an estimated 70% of males. 5 Ophthalmic findings have not been considered part of the classic phenotype of this disease and have received only limited attention in the literature. The disorder is likely unfamiliar to many ophthalmologists. Two reports have mentioned ocular findings in males from families with Danon disease, but detailed descriptions of the ocular phe- notype in Danon disease have not been published. Laforet et al 6 described a patient with decreased visual acuity and a “bilateral maculopathy” and Lacoste-Collin et al 7 reported another patient with decreased vision and a “diffuse choriocapillary atrophy.” We are unaware of descriptions of ocular manifestations of disease in females. Herein we describe the ophthalmic findings in 2 males with Danon disease along with the discovery and description of eye disease in females. Materials and Methods Seven patients with Danon disease were examined in the authors’ university-based retina practice. Five females and a male from a single family were examined as well as another unrelated male. A retrospective review of the records was performed. Institutional review board exemption was obtained. Originally received: June 17, 2005. Accepted: February 13, 2006. Manuscript no. 2005-481. 1 Department of Ophthalmology, University of Colorado, Aurora, Colorado. 2 Cardiovascular Institute, University of Colorado, Aurora, Colorado. Presented as a poster at: American Academy of Ophthalmology meeting, October 2005, Chicago, Illinois. Correspondence to Dr Naresh Mandava, 1675 North Ursula Street, PO Box 6510, Mail Stop F731, Aurora, CO 80045-0510. 1010 © 2006 by the American Academy of Ophthalmology ISSN 0161-6420/06/$–see front matter Published by Elsevier Inc. doi:10.1016/j.ophtha.2006.02.030