Clinical and epidemiological features of keratoconus genetic and external factors in the pathogenesis of the disease.

Clinical and epidemiological features of keratoconus (KC) were studied in a series comprising all the 212 KC patients treated at Oulu University Central Hospital from 1964 to 1984. Altogether 294 keratoconus patients and relatives were examined ophthalmologically by the author. The prevalence rate of KC needing ophthalmic care was estimated to be 0.03% (75/260,000). The annual incidence was 0.0015% (75/260,000 per 20 years) and remained the same throughout the period studied. 62.7% (133) of the patients were male and 37.3% (79) female. 73% were aged 24 years or younger at the onset of symptoms, the mean age of the males at the first examination being 26.5 +/- 8.2 years, and that of the females 30.6 +/- 13.7 years. Corneal transplantation was carried out on 65 of the 144 patients coming from the area served by Oulu University Central Hospital. Familial KC was found in 19 of the 101 families investigated in the north of Finland (19%) and in 5 of the 58 from the south (9%). The higher frequency of familial KC in the north is probably due to the more pronounced effect of gene pooling in the larger families (mean family size 4.9 persons as compared with 3.5 in the south). The inheritance was found to be attributable to a dominant autosomal mode in 24 out of 28 multiple-case families (85%), the disease being inherited from the mother in 15 cases and the father in 9. Data on the order of birth of keratoconic children were obtained from 159 families. 169 out of a total of 688 children were affected (25%). If families with only one child were excluded, then 47 of the 149 first children (32%) and 44 of the 149 second children (30%) had KC. Thus the disease is characterized by incomplete penetrance and variable expressivity. 122 HLA-A,B,C antigen typings were performed in 18 multiple-case families and the HLA genotypes expressed as haplotypes. In 15 families with more than one child affected, 27 keratoconic children were noted to share the mutual haplotype with the affected parent, whereas 3 had inherited the mutual haplotype from the healthy parent (p less than 0.001). The HLA haplotype could thus serve as a marker for KC inside the family. Connective tissue symptoms and abnormalities were seen in 31 out of 46 KC patients (67%) and in 60 out of 122 first-degree relatives from the town of Oulu and its surroundings (49%).(ABSTRACT TRUNCATED AT 400 WORDS)