O-110: Genetic testing for the FMR1 premutation in young women with spontaneous premature ovarian failure

Abstract

To assess the informational needs of women with spontaneous premature ovarian failure regarding genetic testing for the FMR1 premutation. Fragile X syndrome, a cause of mental retardation, occurs when the CGG repeat number in the 5′ untranslated region of the FMR1 gene exceeds 200. Although carriers of the FMR1 premutation (more than 55 but less than 200 unmethylated CGG repeats) were previously thought to be unaffected, women who have the premutation are at increased risk for spontaneous premature ovarian failure. The FMR1 premutation has been found in about 2% of women with no family history of either fragile X syndrome or of premature ovarian failure. This low prevalence, combined with the significant implications of a positive test, creates uncertainty as to the best approach to FMR1 testing in these women. Retrospective. We recruited women with a diagnosis of spontaneous premature ovarian failure. Women seen between June 2004 and March 2006 comprised the study subjects. All women received a 30 minute genetic counseling session that informed them about the relationship between premature ovarian failure and the FMR1 premutation, the availability of FMR1 premutation testing, and the potential implications of a positive test result for the patient and her family. About a month after their visit we telephoned patients to discuss results. Later, under an approved protocol, an individual not involved with the genetic counseling telephoned patients to administer a 15 minute structured interview. Patients were informed that once the interview was completed their name would not be associated with the answers. Thus, responses were anonymous to the team evaluating the findings. Of the 121 patients who received FMR1 counseling during the study period 93 participated in the interview (93/121, 77%). Prior to their visit a majority of women (56/93, 60%) had never heard of the fragile X syndrome or the FMR1 gene. A majority did not know that abnormalities in the fragile X gene could be a cause of the premature ovarian failure (65/93, 70%). Most (84/93, 90%) did not recall ever having been advised to be tested for an abnormality in the FMR1 gene to determine if this could be the cause of their premature ovarian failure. Most women (74/93, 80%) reported that the amount of information provided by the 30 minute genetic counseling session was about right; 7/93 (7.5%) reported that it was more information than they wanted and 8/93 (8.6%) reported that it was less than they wanted. Most women (71/93, 76%) reported that 30 minutes was about the right amount of time for the genetic counseling session; 8/93 (8.6%) reported that it was more and 9/93 (9.7%) reported that this was less time than they wanted. After the 30 minute counseling session nearly all women 90/93 (97%) elected to be tested for FMR1 premutation. None regretted having the test done, including 4 women who had an abnormality detected. Most women cited wanting to know the cause of their premature ovarian failure as the most important reason to be tested (54/93, 58%). Nearly all women with spontaneous premature ovarian failure elect to be tested for premutations in the FMR1 gene when genetic counseling and testing is provided to them at no cost. Most women are satisfied with the amount of information that can be provided in a 30 minute genetic counseling session.