An association among blepharophimosis, resistant ovary syndrome, and true premature menopause

Four cases are described of a very rare association among blepharophimosis, resistant ovary syndrome, and true premature menopause. Plasma levels of follicle-stimulating hormone and luteinizing hormone were significantly elevated and estradiol significantly decreased in all four cases. Ovarian biopsies demonstrated large numbers of unstimulated primordial follicles in three cases and no follicles in one case. Two of the four women were sisters, with the older having true premature menopause and the younger having resistant ovary syndrome. The explanation for the association of blepharophimosis with primary ovarian dysfunction is unknown, but the possibility of a microdeletion of genetic material containing two geographically associated but independent genes could not be confirmed or excluded by high-resolution chromosome banding. All families affected by the autosomal dominant condition of blepharophimosis should be counseled about the high incidence of ovarian dysfunction and female infertility, at least in one form of the syndrome.