Inheritance of Endothelial Dystrophy of the Cornea

Abstract

64 families containing a proband with corneal endothelial dystrophy were examined in order to study the hereditary nature of the disease. Data concerning the frequency of occurrence, severity of the disease, ratio of affected females to males, relationship of the disease with age, and other factors were the subject of a previous report. 7 pedigrees which reflect features of endothelial dystrophy within the 64 families are presented. These features include multiple females in a family being affected, multiple consecutively affected generations, the occurrence of offspring with disease more severe than the parent, and endothelial decompensation (edema) at a relatively young age (less than 40 years of age). The importance of examining family members whenever possible rather than relying on history alone is emphasized. A statistical analysis of the inheritance pattern was performed. Endothelial dystrophy does not seem to follow a strict autosomal dominant pattern even though superficial inspection suggests autosomal dominant inheritance (both males and females affected, successive generations affected, 38% of relatives over the age of 40 years affected). Even though we were unable to determine a specific genetic mode of inheritance in these 64 families with endothelial dystrophy, we do feel that endothelial dystrophy is at least in part an inherited disease. Future investigations might prove sex-linked dominance, genetic heterogeneity, the influence of environmental factors, or a multifactorial etiology.

Prevalence of Primary Cornea guttata and Morphology of Corneal Endothelium in Aging Japanese and Singaporean Subjects

“…The average rate inclusive of all generations was 55%, and there were no differences between Blacks and Whites. Krachmer et al [15] reported a prevalence of 4-70% according to aging. The methodologies for the determination of cornea guttata differed between these reports; however, the prevalence of cornea guttata still appears much higher than in Japan.…”

A Common Trinucleotide Repeat Expansion within the Transcription Factor 4 (TCF4, E2-2) Gene Predicts Fuchs Corneal Dystrophy

“…[4], [5], Other than smoking and a low body mass index, there is little evidence that environmental or modifiable risk factors play a role in the natural history of the disease. [7] Mild disease is asymptomatic, whereas visual loss from severe disease is treatable only by corneal transplantation.…”

Comprehensive Assessment of Genetic Variants WithinTCF4in Fuchs' Endothelial Corneal Dystrophy

“…FECD is an autosomal dominant, 19 late onset disease with a prevalence that is similar to the frequency of the TNR expansion in the general population. 20,21 These considerations suggest that the repeat could be pathogenic through a gain-of-function mechanism.…”