Abstract
Purpose :
Seventy percent of Fuchs’ endothelial corneal dystrophy (FECD) cases in the United States are associated with the CTG18.1 trinucleotide repeat expansion in the transcription factor 4 gene (TCF4). The mutant CUG repeat RNA from this gene locus has been implicated as the cause of the disease. The purpose of this study is to describe an unusual patient case presentation and review other cases from the University of Texas Southwestern (UTSW) FECD Cohort with bi-allelic repeat expansions in TCF4.
Methods :
A 65-year-old Caucasian male with a history of FECD presented with 4 months of bilateral blurred vision and photophobia after undergoing cataract extraction with intraocular lens implant in both eyes. The patient’s visual acuity was 20/200 in the right eye and hand motions in the left eye. On exam, both corneas had multiple epithelial bullae and marked stromal edema with patchy Descemet’s membrane detachments. Anterior segment optic coherence tomography demonstrated a markedly thickened Descemet’s membrane with multiple areas of detachment and areas of posterior lamellar separation. DNA from peripheral blood was used to detect expanded CTG18.1 alleles using a combination of short tandem repeat (STR) analysis and triplet repeat primed (TP) PCR assay. Patient underwent bilateral Descemet's stripping automated endothelial keratoplasty (DSAEK). The explanted tissue was submitted for histopathology and fluorescence in situ hybridization (FISH) for the detection of CUG repeat RNA foci. We reviewed the UTSW FECD Cohort for other subjects with bi-allelic repeat expansions of ≥40 CTG repeats.
Results :
The patient improved after bilateral DSAEK based on visual acuity, exam findings, and imaging. Genotyping based on STR and TP-PCR assays revealed two expanded CTG18.1 alleles. Pathology demonstrated marked, diffuse thickening of Descemet’s membrane at 28-30 microns in the right eye and 30-48 microns in the left eye. FISH confirmed the presence of RNA foci in the explanted corneal tissue. Demographics and modified Krachmer grade disease severity of 18 other probands in UTSW FECD Cohort with bi-allelic repeat expansions are presented for comparison.
Conclusions :
Our patient with bi-allelic TCF4 repeat expansions had an unusual clinical presentation of bilateral detachments of markedly thickened Descemet’s membranes after cataract surgery. Bi-allelic TCF4 repeat expansions may contribute to risk propensity for FEDC.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.