Purpose: To describe the clinical spectrum, the histopathologic findings obtained from one corneal button, and the genetic mapping of an X-linked endothelial corneal dystrophy (XECD).
Design: Observational case series and experimental study.
Methods: We examined a total of 60 members of a family with this dystrophy at the slit-lamp. Light and electron microscopic findings of the corneal button were recorded following one male patient's penetrating keratoplasty. A panel of 25 microsatellite markers covering the X chromosome was typed in genomic DNA from 50 family members. The data were analyzed using the ALLEGRO program to obtain two-point and multipoint likelihood of the odds (LOD) scores and to generate haplotypes.
Results: A total of 35 trait carriers were identified in four generations of the family. Nine male patients demonstrated severe corneal opacifications: two congenital corneal cloudings in form of ground glass, milky appearance and seven subepithelial band keratopathies combined with endothelial changes resembling moon craters. Twenty-two female and four male patients disclosed only endothelial alterations resembling moon craters. No instance of male-to-male transmission of the disease was encountered in the family. Light and electron microscopy disclosed focal discontinuities and degeneration of the endothelial cell layer and marked thickening of Descemet's membrane. Multipoint analysis showed linkage with a maximum LOD score of 10.90 between markers DXS8057 and DXS1047.
Conclusions: To the best of our knowledge, this represents the first fully documented report of X-linked inheritance of an endothelial corneal dystrophy. Late subepithelial band keratopathy is a landmark of XECD. A locus for this corneal dystrophy maps to Xq25.