Parents of Patients With Congenital Hereditary Endothelial Dystrophy Should Be Evaluated for Fuchs Endothelial Corneal Dystrophy
Congenital hereditary endothelial dystrophy (CHED) and Fuchs endothelial corneal dystrophy (FECD) are the 2 common types of endothelial dystrophy seen in the Indian population. Several genes have been implicated as playing a pathogenic role in the corneal endothelial dystrophies.1 Homozygous mutations in SLC4A11 have been implicated in CHED.2–4 In addition, a few studies from various populations have identified mutations in SLC4A11 in late-onset FECD, and approximately 3%–4% of patients are heterozygotes for various pathogenic changes.5–7 This suggests that there is a genetic overlap between the 2 endothelial disorders, with a possible dosage effect of the mutation; loss of function of both alleles of SLC4A11 leads to the severe phenotype of CHED, whereas loss of function of 1 allele, with consequent haploinsufficiency, is associated with the milder phenotype of late-onset FECD. Because parents of CHED-affected individuals are certain to be heterozygous carriers of SLC4A11 mutations, we investigated such families for signs of FECD in the parents. Here, we report 10 families in which the child had CHED and either 1 or both parents revealed characteristic features of FECD.
Eleven children (2 were siblings) of 10 families were brought by parents with complaints of corneal haze with poor vision in both eyes since birth. Clinical diagnosis of CHED was made. The parents of the child were also examined in the clinic as a part of routine examination. Photograph documentation and specular microscopic imaging of the parents were performed when needed. Either 1 or both parents had features of FECD, but all were asymptomatic at the time of examination. In 6 families, the mother had central guttae, in 2 families, the father had guttae, and in the other 2 families, both parents were affected (in 2 families, only the mother was available for examination and was affected). Ten children had keratoplasty (Descemet stripping endothelial keratoplasty in 9 and penetrating keratoplasty in 1) in both eyes with good outcomes. Figure 1A–G shows the clinical photographs and specular microscopic imaging of 1 family in which the child with CHED had both parents showing features of FECD.
Our observation in the 10 families supports the idea that CHED and FECD are causally related. Genetic analysis of the probands and their parents will help in knowing the mutations in these families. It is emphasized that the parents of patients with CHED be routinely evaluated to rule out FECD.