Implications of retinal imaging for identification of Danon disease patients

Abstract

Purpose : Danon disease is a rare X-linked disorder caused by mutations in the lysosome-associated membrane protein 2 (LAMP2) and is typically characterized, in males, by cognitive deficit, cardiomyopathy and myopathy. The trait has also variable expression in the eye, typically pigmentary retinopathy. To further explore the ocular phenotype of Danon disease we describe retinal findings in male and heterozygous female patients. Moreover, we also report findings in an asymptomatic female with somatic mosaicism for a de novo LAMP2 mutation.

Methods : Seven individuals (3 male patients, 3 female patients, and 1 somatic mosaicism mutation carrier) from three families, each carrying a different LAMP2 mutation, underwent comprehensive ophthalmological examination including fundus photography, automatic perimetry, high resolution spectral domain optical coherence tomography (SD-OCT) and autofluorescence imaging.

Results : Abnormal retinal pigment distribution was present in all six Danon disease patients. Observed changes in our cohort were consistent with salt and pepper retinopathy with corresponding zones of hyper and hypofluorecence on autofluoresence imaging. SD-OCT revealed focal loss of photoreceptors and disruptions of the retinal pigment epithelium layer. The severity of retinal pathology generally increased with age, however females when compared to similarly aged males seemed to be less affected which we attribute to tissue specific patterns of X-chromosome inactivation. While no changes were observed biomicroscopically and in SD-OCT images in the female affected by somatic mosaicism, markedly abnormal areas of fundus hypoautofluorescence were found in her left eye.

Conclusions : As demonstrated in our patient cohort, detailed ocular examination should become an essential part of diagnostic work-up both in males and females suspected of having Danon disease. Given the subtle, yet detectable, abnormality that we were able to identify in the somatic mosaic female carrier, retinal autofluorescence imaging may represent a very sensitive screening tool for diagnosis of Danon disease.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.