Fuchs' endothelial corneal dystrophy (FECD) shows characteristic 'beaten metal' appearance on specular microscopy. The genetic defect most commonly implicated in late-onset FECD is:
- A CTG18.1 trinucleotide repeat expansion in the TCF4 (transcription factor 4) gene ✓
- B Autosomal dominant mutation in TGFBI gene encoding keratoepithelin
- C Loss-of-function mutation in the COL8A2 gene encoding collagen VIII
- D SLC4A11 gene mutation affecting the bicarbonate transporter in endothelial cells
Explanation
Late-onset Fuchs' endothelial corneal dystrophy (the common form in adults > 50 years) is strongly associated with a CTG18.1 trinucleotide repeat expansion in intron 2 of the TCF4 gene (transcription factor 4, chromosome 18q21.2). This is the most prevalent genetic risk factor, present in approximately 70–80% of late-onset FECD cases. The repeat expansion leads to RNA sequestration and alternative splicing, impairing endothelial cell function and survival. COL8A2 mutations are associated with early-onset FECD (autosomal dominant). SLC4A11 mutations cause autosomal recessive congenital hereditary endothelial dystrophy (CHED). TGFBI mutations underlie granular, lattice, and Avellino dystrophies of the stroma.
Reference: Khurana Comprehensive Ophthalmology, 7th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.