Familial SLC29A3-related histiocytosis with presumed choroidal infiltration: expanding the spectrum of histiocytosis-lymphadenopathy plus syndrome

Abstract

H syndrome (HS) is a rare autosomal recessive histiocytosis caused by biallelic mutations of the SLC29A3 gene. Ophthalmological involvement is not typical in HS, but is a known manifestation of non-Langerhans histiocytoses. We report two adult siblings with genetically confirmed HS who developed bilateral choroidal infiltration, expanding the phenotypic spectrum of SLC29A3-related histiocytosis. The first case was a woman with a history of HS who presented with progressive visual loss and choroidal lesions on imaging. Systemic findings and histological analyses confirmed non-Langerhans histiocytosis without BRAF V600E mutation. This patient's brother, who was previously asymptomatic, had similar choroidal and systemic findings. Both displayed evidence of MAPK pathway activation (phospho-ERK positive) without detectable somatic mutations. These findings expand the phenotypic spectrum of SLC29A3-related histiocytosis to include presumed choroidal involvement.

Keywords: Choroidal infiltration; ENT3; H syndrome; Non-Langerhans histiocytosis; SLC29A3; Uveitis.