The development of the polycystic ovary syndrome: family history as a risk factor

Three general genetic models for the development of the polycystic ovary syndrome (PCOS) can be proposed, namely: (1) the "single-gene Mendelian" model, which considers the majority of defects present in PCOS to be unique; (2) the "multifactorial" model, which suggests that the defects present in PCOS are not unique, and simply represent the conglomeration of abnormalities already present separately, and to a significant degree, in the general population (e.g. as in cardiovascular disease and non-insulin-dependent diabetes); and (3) the "variable expression-single gene" model, a modified version of the above two. Overall, our data support this third model, suggesting that PCOS is a familial disorder, with a single autosomal dominant gene effect, and a variable phenotype. Family history can then be considered as an important factor determining the risk of developing PCOS. Our preliminary data indicate that a woman's risk of developing PCOS is approximately 40% if her sister is affected. Alternatively, only 19% of mothers were affected, suggesting that the inheritance of PCOS may be preferentially paternal, although expanded clinical studies will be required to confirm these findings. Considering PCOS to be a dominant genetic 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 genetic influences.