A novel frameshift variant in LAMP2 gene mimicking choroideremia carrier retinopathy.

BACKGROUND

Danon disease is a rare, multisystemic X-linked dominant disorder caused by variants in the LAMP2 gene. It can be associated with retinal degeneration, but this is not well characterized. Here we describe a late presentation of a mild retinal phenotype, initially diagnosed as choroideremia carrier, associated with a novel variant in the LAMP2 gene.

METHODS

Retrospective analysis of the case included medical history, ophthalmic examination, multimodal retinal imaging, and microperimetry. Genetic testing was conducted to establish the molecular diagnosis.

RESULTS

A 54-year-old female presented with worsening night vision, without any family history. BCVA was 6/6 bilaterally and fundus examination showed light peripheral pigmentary changes bilaterally. FAF demonstrated a widespread speckled pattern and OCT revealed hyper-reflective spots in the outer nuclear layer. Differentials included non-genetic and genetic causes, suspected of being a manifesting choroideremia carrier. However, initial genetic testing by targeted analysis of retinal disorders did not detect a pathogenic variant. Further systems review revealed that the patient had previously been diagnosed with dilated cardiomyopathy, mini-stroke and partial deafness. Subsequent whole mitochondrial genome sequencing analysis did not detect any pathogenic variants too. Finally, whole exome sequencing with targeted analysis of a panel of hypertrophic cardiomyopathy genes identified a novel pathogenic heterozygous variant (c.925del, p.(Ser309fs)) in the LAMP2 gene, confirming the diagnosis of X-linked Danon disease.

CONCLUSION

Recording previous medical history and extraocular symptoms is crucial. The similarity in choroideremia carrier and Danon disease retinal phenotypes suggests a possible common pathway in these two genes where pathogenic variants lead to retinal pigment epithelium degeneration.