Scoliosis: Causes, genetics, symptoms, and treatment in a southern Italy population

Idiopathic scoliosis (IS) is a largely diffused disease in human population although its pathogenesis is still unknown. There is a relationship between IS phenotype and the patient age, since in the early stage the pathology shows a ratio of 50% between male and female childhood. During puberty the sex mainly involved into manifestation of disease is the female one, suggesting a sex-conditioned manifestation. Genetic inheritance of IS results still unclear although some evidences claim for a recessive multi-factorial inheritance. As far as it concerns the transmission of genetic traits involved in the IS phenotype, we have analysed 72 genealogical trees involving a total of 696 generations and 2416 individuals. For each transmission model we have evaluated using a not parametric analysis the number and percentage of compatible generations, number and total percentage of compatible individuals and number and average percentage of compatible individuals for each family. The results indicate a clear cut for an autosomic recessive trait (H=29.32, df3, p<0.000, Kruskal-Wallis test).There is, however, large agreement in considering the IS as a sex-conditioned disease, in terms of steroid content and their receptor activity. We have, recently, found a possible linkage between the estrogen content and the IS in a teenagers female population of southern of Italy. The 17-estradiol, progesterone and testosterone contents in teens showing the IS phenotype is significantly lower with respect to unaffected girls (P < 0.01, <0.01 and <0.05, respectively). These data support the hypothesis of a reduced steroidogenesis in girls affected by IS. Because other authors have claimed for a linkage between the appearance of IS and some chromosomal region (chromosomes 6 and 10), we have undertaken a study having as target the possible linkage between the IS phenotype and polymorphisms for loci on both chromosomes 6 and 10. The genetic loci we studied were 6p21.3 [17b-hydroxysteroid dehydrogenase (17b-HSD)], 6p21 [3b-hydroxysteroid dehydrogenase (3b-HSD)], 6q25.1 [estrogen receptor a (ERa)], 10q24.3 (17a-hydroxylase), 10q24.31 (21a-hydroxylase) and 10q24.32 (17,20 lyase). Polymorphisms in the coding regions in all gene studied have been found in girls affecting by IS, while the same polymorphisms have not been found in control girls. The 3b-HSD, the 17b-HSD, the 17a-hydroxylase, the 21a-hydroxylase and the 17,20 lyase are enzymes involved in the production of progesterone (3b-HSD), estradiol (17,20 lyase, 3b-HSD, 17b-HSD, 17a-hydroxylase) and testosterone (17,20 lyase, 3b-HSD, 17b-HSD, 17a-hydroxylase), respectively. It is conceivable that the polymorphisms that we have found may have a role in the relationship between the steroidogenetic enzymes (genotype) and the manifestation of IS phenotype, although more functional study on the effects of these polymorphisms could have on the enzyme activity. Among the ERa, we identified four polymorphisms in the exons encoding for the steroid binding domain and two other in the trans-activation domain that could have an effect on the receptor efficiency in binding the ligand in changing the Kd of the receptor protein. The overall data we have obtained, seem to indicate a linkage between the endocrine status and the IS phenotype in the affected girls.