Feasibility of an app-based mindfulness intervention among women with an FMR1 premutation experiencing maternal stress.

BACKGROUND: Women who carry an FMR1 premutation (PM) allele and are mothers of children with fragile X syndrome (FXS) experience elevated maternal stress. In-person mindfulness sessions have been shown to be effective in alleviating maternal stress-related outcomes among mothers of children with intellectual and developmental disabilities. Our prior studies indicate women with a PM are at risk of social anxiety, a potential barrier to in-person mindfulness sessions. AIM: The main goals of this pilot study were to assess feasibility and adherence of an app-based mindfulness training program among mothers of children with FXS and to explore stress, social outcomes, and potential barriers to social support. METHODS: Participants (n = 18) completed questionnaires to assess stress and social anxiety, an app-based mindfulness program, and a semi-structured follow-up interview. RESULTS: Thirteen out of 18 (72%) participants completed the mindfulness program; of those, 10 (77%) found it helpful. Eight out of 18 (44%) participants met criteria for social anxiety and 11 (61%) reported having difficulties reaching out for help when needed. Women with social anxiety and those experiencing barriers to social support were more likely to find the program helpful. CONCLUSIONS: This study provides guidance for future mindfulness-based interventions to alleviate maternal stress in mothers of children with FXS.

Reproductive and gynecologic care of women with fragile X primary ovarian insufficiency (FXPOI).

OBJECTIVE: Approximately 20% of women with a premutation in the FMR1 gene experience primary ovarian insufficiency (POI). We explored diagnostic patterns, frequency of appropriate hormone replacement, obstetric outcomes, fertility treatment, reproductive decisions, and counseling of women with fragile X-associated POI (FXPOI). METHODS: Semistructured interviews with 79 women with FXPOI were conducted by a single interviewer. FMR1 cytosine-guanine-guanine repeat size was determined from a blood, saliva, or buccal sample. RESULTS: The median age of POI onset for women in our study was 33 years. Seventy-two percent of the women had an FMR1 cytosine-guanine-guanine repeat length of 80 to 100. Mean length of time from symptom onset to POI diagnosis was 1.12 years, longer in women with a younger age of POI onset and shorter in women who knew they were carriers. After diagnosis, 52% of women never took hormone therapy, started it years after POI diagnosis, or stopped it before 45 years of age. Forty-nine percent of the women had infertility, but 75% had had at least one genetically related child. Obstetric outcomes were similar to the general population. Forty-six percent of women had a diagnosis of low bone mineral density or osteoporosis, and an additional 19% had never had a bone density assessment. CONCLUSIONS: Women with FXPOI are at significant risk for delayed POI diagnosis and undertreatment with hormone therapy. Although approximately 50% of women had infertility, most were able to conceive at least one child and had no elevated risk of adverse obstetric outcomes.

Fragile X-associated primary ovarian insufficiency: evidence for additional genetic contributions to severity.

The fragile X mental retardation gene (FMR1) contains a CGG repeat sequence in its 5' untranslated region that can become unstable and expand in length from generation to generation. Alleles with expanded repeats in the range of approximately 55-199, termed premutation alleles, are associated with an increased risk for fragile-X-associated primary ovarian insufficiency (FXPOI). However, not all women who carry the premutation develop FXPOI. To determine if additional genes could explain variability in onset and severity, we used a random-effects Cox proportional hazards model to analyze age at menopause on 680 women from 225 families who have a history of fragile X syndrome and 321 women from 219 families from the general population. We tested for the presence of a residual additive genetic effect after adjustment for FMR1 repeat length, race, smoking, body mass index, and method of ascertainment. Results showed significant familial aggregation of age at menopause with an estimated additive genetic variance of 0.55-0.96 depending on the parameterization of FMR1 repeat size and definition of age at menopause (P-values ranging between 0.0002 and 0.0027). This is the first study to analyze familial aggregation of FXPOI. This result is important for proper counseling of women who carry FMR1 premutation alleles and for guidance of future studies to identify additional genes that influence ovarian insufficiency.