Presenter: Maria M. Van Genderen The Netherlands

A 10 year old girl presented with unusual peripheral retinal pigmentations, resembling ‘mud splatter’ The pigmentations were noticed by coincidence, she had no ocular complaints. Her medical history was unremarkable.

Case Summary:

A 10 year old girl presented with unusual peripheral retinal pigmentations, resembling ‘mud splatter’. The pigmentations were noticed by coincidence, she had no ocular complaints. Her medical history was unremarkable, and she had normal intellectual development. Family history was negative for ocular or systemic disease. Visual acuity and visual field were normal. Anterior segments and OCT’s showed no abnormalities. We performed an ERG that showed normal scotopic and photopic responses, i.e. no indication of a retinal dystrophy. Follow-up after two years showed no discernible change in fundus appearance, nor in visual functions.

We thought she might be a carrier of an X-linked condition, notably choroideremia or ocular albinism. Males affected with these conditions show a congenital (ocular albinism) or acquired (choroideremia) depigmented fundus. Because of mosaic expression of the alternative alleles as a result of X-inactivation, carrier females typically show mottled or streaky pigmentations on a light background. Subsequent genetic analysis however did not confirm carriership of an X-linked ocular condition.

At age 19 years, she was referred to the cardiologist because of dizzy spells. She was found to have a severe heart condition: cardiomyopathy with left ventricular hypertrophy, supraventricular tachycardia, and abnormal conductivity. Genetic analysis for cardiac disease showed a de novo mutation in LAMP2.

Lysosome-associated membrane protein-2 (LAMP2) is a lysosomal membrane protein involved in autophagy. Mutations in LAMP2 cause Danon Disease, an X-linked dominant disorder characterized by the classical triad of severe cardiomyopathy, skeletal muscle weakness, and cognitive disabilities. Males are more severely affected than females and usually acquire heart transplantation before the age of 25 years.

In the eye, LAMP2 is expressed in the retinal pigment epithelium (RPE). Retinal abnormalities are seen in about 2/3 of Danon patients. Males usually show retinochoroidal atrophy with complete loss of pigment in the peripheral retina, while females have a peripheral pigmentary retinopathy. Some patients manifest with Bull’s eye maculopathy in association with a cone rod dystrophy. In the majority of patients the ERG is initially normal, but the EOG has an abnormally low standing potential, reflecting the abnormal function of the RPE. Ocular abnormalities increase with age, leading to peripheral visual field loss and decrease in visual acuity.

The patient was treated with an intracardial defibrillator. To date, she experiences no deterioration of visual functions.

In conclusion, peripheral pigmentary retinopathy (‘mud splatter’) may be the first symptom of Danon Disease. Recognition of these characteristic retinal abnormalities is very important, as Danon Disease is a life threatening condition and if untreated may lead to early death.

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