Six different types of OI have been described according to clinical phenotype, molecular genetic analysis and histological findings [1,2,6,7]. Most patients with OI types I-IV, have one of the more than 150 mutations so far described, in COL1A1/COL1A2 genes that encode type I collagen which is the principal matrix protein of bones, sclerae, dentine and ligaments [1,3,8]. Osteogenesis im­perfecta type I is the most frequent form of OI with blue sclerae and autosomal dominant mode of inheritance [1,9-11], and exhibits considerable variability in the number of fractures and degree of disability [3]. Family studies suggest that the severity of disease correlates with reduction in collagen I synthesis [3,12], with the nature of the alteration of the polypeptide chains of procollagen I [1,13-15] and with the modulating effect of some other genes [12, 16,17]. Our patient had a more severe form of OI type I compared with the other affected family members. In 65-80% of cases with KS, serum testosterone is decreased and serum gonadotropins, particularly FSH are increased [4,5]. Klinefelter’s syndrome is often associated with gyneco­mastia, diabetes mellitus, autoimmune disorders, mental retardation or cancer. Taurodontism is a rare disease affecting teeth which occurs in more than 40% of patients with KS, and becomes more pronounced with increase in the number of X chromosomes [4].The combination of OI with the classic XXY form of KS in our patient may explain the difference in OI phenotype from that of the affected members of his family, and suggests the probable role of genes present in gonosomes. It has been established that about 43% of KS patients have increased conversion of total testosterone into estradiol in peripheral tissues, increased binding with SHBG and low free, biologically active testosterone and/or biological effect in the periphery [6,7]. The same mechanism may explain why, despite the normal concentration of testosterone and SHBG, our patient manifested hypogonadism with eunochoid habitus. The X chromosomes in KS patients produce a double gene dose effect because of seldom and incomplete inactivation of one of these during embryonal development. The gene for the androgen receptor is present on the long arm of the X chromosome, whereas genes that take part in the growth and development of bones are on the short arm. The extra X chromosome may explain the normal height and good callus formation in spite of the severe osteoporosis in our patient.The participation of many genes from autosomes and from the X chromosome in bone and skeletal formation and growth requires a complex therapeutic approach. Unfortunately, we could not conduct a molecular genetic study for mutations in the procollagen I.
In conclusion, coexistence of OI and KS in our patient resulted in much more severe demineralization of the skeleton without an effect on the height, stature and callus formation in comparison with the other affected members of the family. Treatment with testosterone and biphos­phonate improved the clinical course and prognosis of both diseases.