**4.2 Basis for ethnic diversities**

A summary of reported studies (**Table 1**) shows in general higher prevalence in Asians than Caucasians, with disease started earlier and severe. But occurrence at Japanese is low. There are also vast differences in the same ethnic group. Environmental factors and investigative criteria other than genetics would affect the reported occurrence of keratoconus. The very wide range of keratoconus prevalence and incidence may be a result of non-uniform diagnostic criteria applied in different studies. Another cause may be genetic variations among different ethnic populations. There is a significant role of ethnicity. Hence rigorous, multiethnic, well-organized, and population-based epidemiological studies with large sample sizes for keratoconus are needed. Nevertheless, in addition to ethnicity, currently reported epidemiologic studies indicate that potential causes underlying higher prevalence of keratoconus could be due to a host of factors including geographic locations, ultraviolet irradiation exposure, consanguinity, persistent eye rubbing and atopy. The etiology of keratoconus is complex, involving multi-factorial interactions of genetic, personal, and environmental factors.


**59**

*Molecular Genetics of Keratoconus: Clinical Implications DOI: http://dx.doi.org/10.5772/intechopen.90623*

**6. Twins and familial segregation**

**6.1 Twins with keratoconus**

**6.2 Familial linkage**

Whether males and females have different prevalence is unclear as inconsistent results have been reported [55]. Disease onset in males tend to be earlier and disease progression faster than female patients in both Asian and Western studies, while gender bias has not been consistent [40, 50, 56, 57]. Male and female sex, did not show difference in prevalence, while gender bias have not been consistent in previous reports. In a Japanese cohort of 90 patients, men were diagnosed younger than women [58]. A questionnaire survey of 670 patients in New Zealand also showed male patients were detected at younger ages than females [59]. In a Turkish cohort of 248 patients, there was no gender difference in cornea properties including central cornea thickness and keratometry parameters [56]. In a study in the USA of 1209 patients from 16 clinics, while there was no difference in disease severity according to keratometry or scarring, less women were had have Vogt striae [57]. Female patients in this study had higher mean age than the males. Overall, there was indication that men developed keratoconus earlier, progressed faster and required more serious treatment.

As early as 1954 occurrence of keratoconus in both identical twins had been reported [60]. Following twins reports in different ethnic groups, one twin pair was found to show different contrast sensitivities [61]. However, two pairs of Caucasian identical twins both showed similar features clinically and under videokeratography and radial keratotomy, as one pair were at early and the other as later stage [62]. Two pairs of monozygotic twins were found discordant for keratoconus in the USA, one from a hispanic family of Mexican descent and the other Caucasian from England [63], while dissimilarity in phenotype may suggest the absence of genetic involvement. However, natural monozygotic discordance could occur if there was separation of the zygote into two distinct cell masses after fertilization before the start of tissue differentiation. Post-zygotic events that lead to existence of two different cell clones in the early zygote may precede the twinning process. In the Mexican family, 39 members were examined and 5 were suspected for keratoconus by corneal topography. Also, one distant relative was a confirmed keratoconus patient. Corneal topography also revealed one suspect from 59 family members examined in the English family. There could be a genetic component in the keratoconus phenotype in these two families [63]. Of note, more and more concordant twins with keratoconus have been reported, including reported concordance in all 13 monozygotic and 5 dizygotic twins [64].

In the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study in a cohort of 1209 patients mixed in ethnicity in the USA, 829 (69%) white, 240 (20%) black, and 99 (8%) Hispanic, family history of keratoconus was reported in 13.5% of the cases [65]. After follow-up for 8 years, the inheritance patterns were not established [66]. In another study from the USA, more females reported family history than males. But it was unclear whether it was a difference in attitude on reporting or a genuine gender difference in familial link [57]. In the New Zealand study, familial aggregation analysis showed keratoconus familial rate of 23.5% [59]. In Scotland, family history occurred in 5% of 186 white patients [67]. In a report from North India among 120 patients, 6 (5%) had family history [68]. In a review of keratoconus

**5. Gender differences**

#### **Table 1.**

*Geographical and ethnical diversities in reported prevalence of keratoconus.*
