Research Update: Experiences of women with the Fragile X premutation

Updated: Apr 3, 2019

It is only fairly recently that research has started focusing on people who have the Fragile X premutation, i.e. individuals who have a smaller expansion of the fragile X gene (FMR1). While it was previously thought that people with the Fragile X premutation were unaffected carriers of the syndrome, recent investigation has led researchers to believe that carriers too might experience certain physiological and psychological symptoms.

While physical effects of the premutation have been previously explored, less is known about how the premutation affects the behavioural traits and mental health of carriers, particularly female carriers. Existing research in this area tells us that some women with the premutation might be more at risk for various mental health concerns like depression, anxiety and social phobia. A small number of women with the premutation (approximately 5%) also meet criteria for a diagnosis on the autism spectrum. Some emerging evidence also suggests that some women with the fragile X premutation might show autistic traits, which are the very subtle characteristics which are otherwise also present in the general population, but which are more frequently observed in individuals with autism and their relatives. This does not necessarily mean that these women with premutation can be diagnosed as autistic, just that they share certain characteristics.

In our recent research study, we collaborated with colleagues at the University of Birmingham with the aim of gaining a better understanding of the psychological characteristics of the Fragile X premutation in women. Additionally, we felt it important to focus our investigation on whether the presence of autistic traits and mental health difficulties might relate to women’s experiences of caring for a child with Fragile X Syndrome. Parenting a child with learning difficulties and challenging behaviour may in itself be a cause of stress, anxiety and depression. We wanted to evaluate whether or not the risk of mental health difficulties or the presence of autistic traits in women with the FX premutation was the same as that reported in mothers of children with other neurodevelopmental disorders.

What did we do?

We invited women under the age of 50 who had the Fragile X premutation to take part in the study. The study focussed only on females, as women with the Fragile X premutation are under-represented in research.

The study was conducted online using various self-report questionnaires. The first part of the online study recorded autistic traits and preferences, anxiety, depression and parenting stress. The reports from mothers of children with Fragile X syndrome – women who themselves have the fragile X premutation (FX mothers) – were evaluated alongside reports from mothers of children with autistic spectrum disorder (ASD Mothers) and mothers of neurotypical children (TD mothers).

The second part of the study evaluated autistic traits, anxiety and depression levels of women with children with Fragile X (FX mothers) to that of women with the fragile X premutation who had no children (FX non-mothers), as well as women with neurotypical children (TD mothers).

Additionally, women with the FX premutation were interviewed over the phone or in person, to gain insight into their subjective day to day experiences, their strengths and the challenges they might face. Women from a wide range of ages were interviewed, some of them mothers of children with FXS or FX premutation, some of them having both TD and FXS children, and some who did not have children. You can read transcripts of some of the women's interviews about living with the FX premutation, by clicking on the links at the bottom of this article.

Autistic traits and preferences

We found that in response to the questionnaire, on average, more autistic traits and preferences were reported by both the FX mothers group and the ASD mothers group. Additionally, the FX mothers group, i.e. the women with fragile X premutation, also reported that they have certain social tendencies which are often associated with the autistic spectrum and were more likely to pay more attention to detail that to the big picture, which too is a characteristic frequently seen in those on the autistic spectrum.

The results also indicated that both FX mothers and FX non-mothers report similar trends in social and attention to detail autistic traits, which leads us to believe that women with FXS premutation, both with and without children, show more autistic traits and preferences than TD mothers.

To understand subjective social preferences of women with the Fragile X premutation, the women interviewed were asked about their childhood and social environments: how they liked spending time with other people, whether or not they were comfortable being the centre of attention, if they had a lot of friends or preferred a smaller group of friends to whom they were close to. While the women who we interviewed did not consider themselves to be excessively shy or have any significant problems in making friends, they consistently reported enjoying being by themselves.

Eight out of the nine women agreed that, although they might have large friendship circles, they often had a smaller group of people they were especially close to:

“I was popular and had lots of friends in primary school, but I tended to like to be in small friend groups rather than large ones. And I think that has probably been the case for the rest of my life”

said one of the women who was interviewed.

Furthermore, when amongst a large number of people, interviewees mentioned that they would not choose to be in the spotlight. Four of the interviewees also mentioned being somewhat socially awkward or nervous in novel social situations:

“When meeting strangers, I overcompensate by talking too much, or I just stop and stare”

said one of the interviewees.

Another interviewee speculated if her social difficulties were related to her premutation:

“I don’t form friendships the same way as ‎other people, and I feel out of the loop of the conversations a little bit… ‎and I have always felt a little bit like that. I always thought it was just me, but I don’t know now ‎if it was actually to do with the fragile X premutation.”

Anxiety and Depression

Both FX mothers and ASD mothers reported higher levels of mental health symptoms in comparison to TD mothers. FX mothers reported experiencing more anxiety related symptoms than depression symptoms. The degree of mental health symptoms also related to the number of autistic traits reported. Additionally, both FX mothers’ and FX non-mothers’ depression and anxiety levels were comparable, and were significantly higher than the TD mothers’. This suggests that the FX premutation in itself, could possibly contribute to their mental health issues and characteristics which are often associated with autism.

During the interviews, inquiries about mental health were met with mixed reactions. While four of the nine women were forthcoming about the mental health issues they had been diagnosed with through the course of their lives, the two mentioned that although they occasionally felt depressed or anxious, they had either never sought professional help. For some of these women who said they did struggle from anxiety and/or depression, the premutation diagnosis helped them to better understand their own mental health issues. One such interviewee said,

“It helped because it started to explain a lot of things. I have a long history of depression and anxiety…. which has increased over the last ten years, ‎so definitely before I had children. I certainly think that this ‎explained a lot to me and made me feel a bit more comfortable about the fact that I struggled for a ‎long time.” ‎

These interviewees speculated if having experienced depression and/or anxiety was different to any neurotypical person facing mental health challenges:

“I can only say it’s possible (that the premutation caused her depression), but I couldn’t say that anyone else might not go through something ‎similar to what I did if they had faced all those circumstances together.”‎

Some of them agreed that the premutation did affect their mental health:

“It took me a long time to acknowledge that was the reason of my depression and ‎anxiety. But I wonder whether that ‎is the case with carriers that don’t have affected children.”

The remaining three of the nine women interviewed were sure that they had never suffered from any mental health issues because of the premutation per say:

“From a mental health perspective, I don’t think I have ever suffered. Obviously, I get down, like ‎everybody feels a little down sometimes in their life, but I have never really suffered from being ‎down until I had the kids and the diagnosis. And I know it is connected to that (the child’s diagnosis) and ‎not anything that I am suffering from.”

Experiences of Parenting

As with autistic traits, anxiety and depression, mothers of children with FXS or ASD were found to be suffering from higher levels of parenting stress than the TD mothers. However, this parenting stress did not appear to be related to either autistic traits, anxiety or depression in FX mothers. This may indicate that the anxiety and depression experienced by the women with fragile X premutation might not be due to caring for a child with their own special needs and challenging behaviour, but that their premutation itself might make them more susceptible (than the general population) to these mental health difficulties.

Effects of finding out about the Premutation

One of the positive aspects of finding out about the premutation, as mentioned by most of the women who were interviewed, was that they could inform their relatives and get them tested as well.

Majority, that is six out of the nine women interviewed agreed that the diagnosis significantly affected their family planning:

“Had I known about this, we would have definitely looked at reproductive choices differently. I knew at that point that if I wanted any other children, I could not just go ahead in the normal way”

said one of the women, who found out about their premutation after their firstborn was diagnosed. Similarly, another interviewee acknowledged:

“(After finding out) I wasn’t having any other children, I would have liked to have a third child, but I can’t do that now”.

One of the interviewees, who had found out about their premutation by the means of one of their relatives getting diagnosed and consequently decided not to have children, said

“We chose not to have kids because I knew if I had gotten pregnant, I would have wanted it. And ‎then deciding to bring a child in the world who could have real difficulties is… is overwhelming really ‎to make that decision.”

However, two of the women insisted that even if they had the knowledge about the premutation before they conceived, it would not have really changed their decision to have children, while on of the interviewees decided to have another child after they found out about the diagnosis.

Four of the interviewees mentioned that finding out helped them spread the word amongst their extended family, which in turn enabled them to make informed choices. All of these women count this as a positive impact of finding out about the premutation, when they did.

Conclusions and future directions

Overall, the women who were interviewed agreed that it was hard for them to comment on whether they thought the FX premutation was responsible for the challenges they faced in life. As one of the interviewees summed it up,

“It is only when you find out that you possibly look back and think, oh ‎was this because I am a fragile X carrier… It is very hard to answer the question because you have ‎never had any other life…”

It can be garnered from the interviews that women with FX premutation have diverse experiences of being a carrier of FXS. While the online research study suggests that women with the premutation, both with and without children, might possess some characteristics which are often associated with the autism spectrum, like social awkwardness, and have possible mental health issues, like anxiety and depression, the interviews show that there is great variation in how the premutation may or may not affect a woman. While for some women the premutation helps explain the mental health challenges they have faced throughout their lives, some women remain unaffected by it.

It is, therefore, all the more important to conduct further research in this area, especially with carrier women who do not have any affected children, in order to distinguish whether the challenges faced by them are due to caring for a child with a neurodevelopmental disorder or if their difficulties are indeed due to their genetic status. Direct face-to-face tests, rather than self-report questionnaires, too would help to reveal any effects that the FX premutation might have on underlying psychological mechanisms. Knowing how the premutation affects a person socially, mentally and physically will, in turn, aid in the development of strategies to help affected women cope most effectively with the challenges associated with it.

Click to download

Click here to read Grace's interview

Click here to read Brianna's interview

Click here to read Lou's interview

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