Tapetal-like sheen as a key phenotypical feature in TTLL5-associated cone dystrophy caused by a novel variant

Abstract

Purpose

To report a patient with cone dystrophy and a striking tapetal reflex caused by a novel variant in TTLL5, which was initially missed by a local retinal specialist due to inaccurate phenotyping of macular dystrophy.

Observation

A 33-year-old male patient presented with Bull's eye maculopathy and a tapetal-like reflex, confirmed via fundus examination and multimodal imaging. Initial genetic testing with a macular dystrophy panel was negative. Electroretinography showed reduced photopic responses and normal scotopic responses, supporting a diagnosis of cone dystrophy, and subsequent evaluation using an extended inherited retinal dystrophy panel identified a homozygous TTLL5 c.1186+2T>C variant classified as “likely pathogenic.”

Conclusions and importance

This case underscores the critical role of accurate phenotyping in guiding molecular genetic testing, particularly in distinguishing cone dystrophy from other macular dystrophies, and highlights the unique expertise of inherited retinal disease specialists in this process. Additionally, it further validates the possibility that the tapetal reflex is a common but previously underrecognized feature of TTLL5-associated retinal dystrophies and expands the known variant spectrum of TTLL5-associated disease. The presence of a tapetal reflex—previously widely associated with RPGR-associated dystrophies—highlighting the overlapping disease mechanisms and clinical presentation.