Female carriers of fragile X premutations have no increased risk for additional diseases other than premature ovarian failure.

Carriers of fragile X premutations were previously considered phenotypically normal but are now known to be at risk for premature ovarian failure (POF). This prompted us to investigate whether premutation carriers (PC) have an increased risk for other diseases. We approached 306 women out of 84 fra(X) families of whom 264 (86.3%) participated in this study. A medical history was taken of these women. Whenever possible, the anamnestic data were verified with medical records. We first evaluated the occurrence of diseases that are commonly associated with menopause in PC and compared this to that in women with either a normal FMR-1 gene or a full mutation. We found no statistically significant differences in the occurrence of diseases known to be associated with menopause, such as cardiovascular diseases and osteoporosis. However, lower bone mineral density was observed only in PC. Subsequently, we compared the occurrence of other medical problems between the two groups by estimating relative risks. PC did not demonstrate other diseases more commonly compared to non-PC from the same families. These findings are important for the counseling of PC. Carriership of the premutation may affect the ovaries, but does not substantially increase the risk for additional medical problems. Once a PC does experience POF, she is at risk for early estrogen deprivation, which may lead to a premature decrease in bone density, when not treated.