Objective: To report the clinical, functional, and in vivo microanatomic characteristics of a family with choroideremia with a deletion of the entire gene that encodes for the Rab escort protein 1 (CHM).
Methods: We performed clinical examination, flash electroretinography (ERG), light- and dark-adapted perimetry, and optical coherence tomography; reviewed medical records; and obtained the medical history of the proband and 3 other family members.
Results: At 4 years of age, the proband had a hypopigmented fundus and retinal pigment epithelium mottling, and dark-adapted ERGs were reduced. Severe retinal pigment epithelium and choriocapillaris atrophy developed by 6 years of age, paralleled by a lesser ERG decline. Optical coherence tomography findings showed normal neural retinas overlying mild changes in the retinal pigment epithelium and thinned neural retina with impaired lamination, yet the neural retina was fairly preserved over retinal pigment epithelium and choriocapillaris atrophy. The carrier mother had diffuse elevation of 650-nm dark-adapted thresholds.
Conclusions: Deletion of the CHM gene causes severe choroideremia. Results of serial ERGs and fundus examinations documented progression first of rod and then of cone disease. Fundus appearance deteriorated rapidly, in excess of the severity of the ERG decline. Optical coherence tomography findings explained this observation, at least in part.
Clinical relevance: To our knowledge, this is the earliest clinical, microanatomic, and ERG longitudinal phenotypic documentation in molecularly characterized choroideremia and the first documentation of impaired dark-adapted cone function in carriers. The preservation of the neural retina has mechanistic, prognostic, and therapeutic implications.