THE DEVELOPMENT OF THE POLYCYSTIC-OVARY-SYNDROME - FAMILY HISTORY AS A RISK FACTOR

Three general genetic models for the development of the polycystic ova ry syndrome (PCOS) can be proposed, namely: (1) the ''single-gene Mend elian'' model, which considers the majority of defects present in PCOS to be unique; (2) the ''multifactorial'' model, which suggests that t he defects present in PCOS are not unique, and simply represent the co nglomeration of abnormalities already present separately, and to a sig nificant degree, in the general population (e.g. as in cardiovascular disease and non-insulin-dependent diabetes); and (3) the ''variable ex pression-single gene'' model, a modified version of the above two. Ove rall, our data support this third model, suggesting that PCOS is a fam ilial disorder, with a single autosomal dominant gene effect, and a va riable phenotype. Family history can then be considered as an importan t factor determining the risk of developing PCOS. Our preliminary data indicate that a woman's risk of developing PCOS is similar to 40% if her sister is affected. Alternatively, only 19% of mothers were affect ed, suggesting that the inheritance of PCOS may be preferentially pate rnal, although expanded clinical studies will be required to confirm t hese findings. Considering PCOS to be a dominant generic disorder with a high degree of expressivity, we propose that the risk of developing the disorder is governed by family history and the degree of exposure to the selected environmental and/or other generic influences.