A Prospective Study of Filaggrin Null Mutations in Keratoconus Patients with or without Atopic Disorders

Background: Atopic dermatitis (AD) is significantly associated with keratoconus (KC). An inherited component for KC has been suggested. Filaggrin (FLG) mutations are a strong genetic risk factor for AD. Since filaggrin is also expressed in the corneal epithelium, we hypothesized a common aetiology for ichthyosis vulgaris (IV), AD and KC. Objectives: We examined the prevalence of AD and IV in a KC population. We also studied the expression of filaggrin in normal and KC cornea and analysed 2 prevalent loss-of-function FLG alleles (R501X and 2282del4) in a KC population. Finally we examined whether the population with KC and FLG mutations had specific clinical characteristics. Results: Of 89 KC patients, 38 had current or a history of AD and/or IV. Five patients were carriers of at least 1 FLG mutant allele and had a clinical diagnosis of AD and IV with a severer KC. Conclusion: The low frequency of FLG mutations is surprising since 42.7% of our KC population had AD associated or not with IV; the expected frequency would have been 12–15%, based on our previous studies. Further studies are required to look at other possible FLG mutations or other candidate genes.