Turner syndrome and female sex chromosome aberrations: deduction of the principal factors involved in the development of clinical features

Abstract

Although clinical features in Turner syndrome have been well defined, underlying genetic factors have not been clarified. To deduce the factors leading to the development of clinical features, we took the following four steps: (1) assessment of clinical features in classic 45,X Turner syndrome; (2) review of clinical features in various female sex chromosome aberrations (karyotype-phenotype correlations); (3) assessment of factors that could lead to Turner features; and (4) correlation of the clinical features with the effects of specific factors. The results indicate that the clinical features in 45,X and in other female sex chromosome aberrations may primarily be determined by: (1) degree of global non-specific developmental defects caused by quantitative alteration of a euchromatic or non-inactivated region; (2) dosage effect of a pseudoautosomal growth gene(s), a Y-specific growth gene(s), and an Xp-Yp homologous lymphogenic gene(s); and (3) degree of chromosome pairing failure in meiocytes that are destined to develop as oocytes in the absence of SRY. 1991; Grumbach and Conte 1992). However, the pertinent factors have not been determined to date. The method to clarify the factors responsible for the development of the Turner phenotype can be broken down into the following steps: (1) assessment of clinical features in classic 45,X Turner syndrome; (2) review of clinical features in various female sex chromosome aberrations (karyotype-phenotype correlations); (3) assessment of factors that could lead to Turner features; and (4) correlation of the clinical features with the effects of specific factors. If the clinical features in 45,X and in other female sex chromosome aberrations are explained by the effects of specific factors, it can be said that such factors contribute to the development of Turner features. In this paper, we take each of the above steps, and propose the principal factors involved in the development of clinical features in Turner syndrome.