Familial Keratoconus

Abstract

Abstract: : Purpose: To determine the inheritance pattern of familial keratoconus. Methods: Patients with a family history of keratoconus were recruited and pedigrees drawn. Participants in this study (affected and unaffected) were examined by slit–lamp biomicroscopy and videokeratopography (Orbscan II). Blood samples were taken for further genetic studies. Patients with forme fruste disease were included as affected. Results: 110 families with a total number of 273 affected individuals were identified with a male to female ratio of 1.48. 66 families were reported to have at least one affected member in two or more successive generations, or two affected members in different family branches, favoring an autosomal dominant (AD) mode of inheritance. In two of these families only males were affected and as the disease was transmitted by females, x–linked inheritance was considered. In 46 families only one generation was affected and the mode of inheritance could not be determined. Five sets of twins were identified in pedigrees where an additional family member was affected: one set of monozygotic twins that was concordant for keratoconus, and four sets of dizygotic twins, two of which were concordant, one disconcordant, and in one set the second twin has not been examined. A further five sets of monozygotic twins were identified in pedigrees with no other family member with keratoconus: four were concordant for the disease, and in one set the second twin has not be examined. Conclusions: Genetic factors play an important role in the pathogenesis of keratoconus. This is confirmed by the number of families with more than one affected member and by the high concordance rate in monozygotic twins. The most common inheritance pattern seems to be autosomal dominant. The significance of forme fruste disease in pedigree analysis needs to be clarified.

Keywords: keratoconus • genetics • cornea: clinical science