Posted at June 26, 2013 | By: | Categories: Treatment and Intervention | 39 Comments

What Defines a “Carrier”?

Everyone has his burden;
what counts is how you carry it.
–Joe Brown and David Brown
In my role as a genetic counselor, I frequently meet with women who have Fragile X pre- or full mutations. Most of these women are typically functioning mothers who found out about their own Fragile X mutations only after they had a child affected by fragile X syndrome. Whether they have pre- or full mutations, we generally refer to such mothers as “carriers.”Collage 3

The term “carrier” is problematic, however, since in genetics, it generally refers to someone who has a gene mutation without showing any symptoms. We now know that some women with premutations have infertility or fragile X-associated tremor ataxia syndrome (FXTAS), while those with full mutations may have learning or psychiatric issues.

I know many women with Fragile X full mutations who have average or above average intelligence with only mild manifestations of the gene expansion, such as excessive shyness or a lifelong difficulty with math.

We also use the term “carrier” for men who have Fragile X premutations, even though many of them will eventually go on to develop symptoms of FXTAS. Although the term “carrier” is not technically correct for people who have symptoms, in the Fragile X world, we generally use it to describe individuals with unimpaired intellectual functioning, regardless of whether they have pre- or full mutations.

Why is there so much variability among male and female Fragile X carriers? There are a number of factors involved. Because the Fragile X gene is X-linked, gender plays a big role in determining who might show symptoms. Male premutation carriers, because they have only one X chromosome, are much more commonly affected by FXTAS than are female carriers. Females have two X chromosomes, so even when they carry a Fragile X premutation on one of them, they have a second copy that can significantly reduce their risk of developing FXTAS.

On the other hand, because men don’t have ovaries, they are at not at risk for developing fragile X primary ovarian insufficiency (FXPOI), a condition that affects only women and is associated with hormonal symptoms such as irregular periods, infertility, and early menopause. Only premutation carriers are at risk for developing FXTAS and FXPOI; these conditions do not affect males or females with full mutations.

Another factor that influences carrier symptoms is the amount of FMRP (Fragile X protein) a gene produces. Typically, male and female premutation carriers have normal amounts of FMRP and do not have intellectual symptoms. A Fragile X gene with a full mutation usually does not produce FMRP, and this leads to fragile X syndrome in almost all males and many females who have full mutations.

In some females with full mutations, however, their second X chromosome does a good job of compensating for the missing protein, and they show minimal to no intellectual symptoms. Such females are “carriers” who can pass the gene mutation to their children but who themselves show few effects.

Fragile X inheritance is particularly complicated compared to other genetic disorders, so it’s no surprise that families often have difficulty understanding where one draws the line in defining who’s a “carrier.” Even the scientific community has marveled at the way the Fragile X story has unfolded, going from a straightforward X-linked cause of intellectual disability in boys to a highly complex adult onset condition.

Twenty years ago, no one would have guessed that a single gene disorder could manifest itself in so many different ways, from autism and learning issues to infertility and balance problems. Different symptoms present themselves in different ways and to varying degrees over the lifespan. As one carrier mother once described it, “Fragile X is the gift that keeps on giving.”

Fragile X isn’t the only condition that has genetic counselors questioning the definition of the term “carrier.” With the completion of the Human Genome Project in 2003 and the many advances in genetic testing that followed, we now know about many genes that have subtle effects or that predispose individuals to developing problems later on. Actress Angelina Jolie recently made news when she decided to undergo a double mastectomy because she carried a gene that caused breast cancer in her mother and other family members. Other genes have been found that predispose carriers to behavioral differences, such as ADHD and mental illness.

It is estimated that every human carries anywhere from a handful to dozens of mutations or other genetic differences that have the potential to cause medical, developmental, or psychiatric disabilities in themselves and/or their children. Most people go through life never knowing which genes they carry unless they happen to develop a hereditary health problem or have a child with a genetic condition. It may be that Fragile X carriers have no greater number of gene mutations than anyone else in the population, but for various reasons, they come to discover that one of their genes is a Fragile X mutation. With knowledge comes power, and in that sense, carriers have a unique window into their genetic destiny.

Brenda Finucane, MS, CGCBrenda Finucane, MS, CGC
is the NFXF Genetics Consultant, a member of the NFXF’s Scientific and Clinical Advisory Committee, and serves as the associate director of Geisinger Health System’s Autism and Developmental Medicine Institute in Lewisburg, PA.


  • Thank you for this article you have answered a few questions that I have always wondered about. Especially about early menapause which I as a carrier started in my 40’s.

  • It was July 21, 1988 when a doctor in developmental and behavioral pediatrics so compassionately and so very kindly said to me the words you used in your last paragraph. I have never forgotten those words nor the doctor who is now deceased. it was my first time hearing the term FX Syndrome as well. Thanks for your words, also.

  • I remember when I was having my second CVS procedure and the director of the genetics dept. at this VERY prestigious university said to me, “well, if you are having a girl she will not be affected, she will be a carrier. ” I was furious. I tried to explain to this so called expert that the way I found out our family has Fragile X is that my female first cousin has MR and a variety of psychiatric issues related to Fragile X. He said that Fragile X does not usually produce symptoms in girls and I really should not worry about that. All of the women in my family who are so-called “carriers” have symptoms. Genetics professionals who dismiss that are making a mistake.

    • Brenda Finucane (NFXF Team Member)

      July 11, 2013 at 1:08 PM (Reply)

      Your experience with getting misinformation about fragile X from medical professionals is not unusual. For decades, fragile X was thought of as a condition that solely affected males with developmental disabilities. The NFXF and the fragile X community have worked hard to correct this misconception about fragile X; but we all still need to educate professionals and the general public about the wide range of fragile X symptoms among males and females.

  • Unfortunately, not too many women with pre mutations have much support when finding out they are a carrier of Fragile X. I was misdiagnosed in my mid 20’s by my OB/GYN doc after performing multiple test because I was having menopause like symptoms. He told me that I was “just going through menopause” and I was not given any explanation as to why. Fortunately I already had two children when I was told that I most likely could not have children. It wasn’t until I was in my early 30’s that I was actually tested for Fragile X because a relative came forward with the information that another family member had Fragile X. I feel that more physicians need to be educated about the symptoms of both pre and full mutation fragile X so that they can correctly diagnose patients. It can be devastating news to someone at such a young age that they can most likely “not have children” or that their children could have Fragile X.

  • Thank you for the information. However, it leads me to a new question. You mentioned “only premutation carriers are at risk for developing FXTAS and FXPOI; these conditions do not affect males or females with full mutations.” Can you provide some information on why premutation carrier women, (but not full mutation) are at risk for FXTAS ? It seems odd (counter-intuitive) that a premutation would have a risk for a FraX condition that a full mutation doesn’t. As a premutation carrier, is there anyway for me to know my risk of FXTAS, and ways I can mitigate it ?

    • Brenda Finucane (NFXF Team Member)

      July 11, 2013 at 1:21 PM (Reply)

      Your question is a common one, and like everything else about fragile X, the answer is a little complicated! Although FXTAS and FXPOI involve changes in the same gene as FXS, the reasons these conditions develop is quite different. FXS primarily results from a lack of fragile X protein (FMRP) when a person has a full mutation. Individuals with premutations generally produce plenty of FMRP, but because their premutations have to work extra hard to make FMRP, they produce too much of a different body chemical known as “messenger RNA” (mRNA). Only people with premutations have a problem with too much mRNA, and this is thought to cause symptoms of FXPOI and FXTAS over time. Males and females with full mutations do not over-produce mRNA, but they don’t make FMRP which is what causes FXS. This is also why treatments that target the underlying cause of FXS will not benefit people with FXTAS and FXPOI.

  • Thank You for your insight! I want to learn all I can about Fragile X,having 2 grand children that have this,and I want to help in every way!

  • I just read this article and would like to know more. I have a son with Fragile X and several siblings and other relatives. We have figured out that it came from my mother’s side of the family. We assumed that since it came from my side of the family and my son has it that I must be a carrier and gave it to him. I have never been tested. It has come up lately that maybe I more than carry it, that I could actually have FX. I’m 50 years old and wonder what difference would it make at this time in my life. Yet reading the article makes me wonder because I have demonstrated some of the symptoms mentioned. Can you start out as say a carrier and then develop into a pre mutation or full mutation? And what does that mean exactly? I am embarrassed to admit even after all these years of having FX syndrome as a part of my life, I still don’t completely understand it. My son was diagnosed when he was 9 and he is 24 now. Can anyone help me, steer me in the direction to learn and understand more? Thanks

    • Brenda Finucane (NFXF Team Member)

      July 11, 2013 at 1:42 PM (Reply)

      Many women have asked the same question – you are not alone and there is no need to feel embarrassed! Fragile X is among the most complex genetic disorders to understand in terms of its inheritance and symptoms. To answer your first question, because you have a son with fragile X syndrome, we know that one of your X chromosomes has a fragile X mutation. The reason we can be sure, even without testing you, is that boys never inherit an X chromosome from their fathers. The other thing we know is that a male’s full mutation always comes from a mom’s X that has a fragile X mutation. The question that DNA testing can answer is whether your X has a premutation or a full mutation. That answer could be important for your own health monitoring, since as you’ve read, some women with premutations may develop symptoms of FXTAS after 50, for example. Before considering testing, I suggest that you meet with a certified genetic counselor to discuss your family history and the indications for DNA testing for you and possibly other relatives. You may have met with a genetic counselor when your son was first diagnosed, but in my experience, many parents benefit from a “refresher course” later on after they are over the initial shock of the diagnosis. There’s so much to know about fragile X, it’s very difficult to understand all aspects of it in one appointment. To locate a genetic counselor in your area, go to and search under the “Find a genetic counselor” link.

  • Great article but what about all the carriers who live day to day with constant pain, often diagnosed as fibromyalgia or with autoimmune disorders like arthritis and lupus? There must be someone who can study this as t seems tone far too coincidental that so many women suffer on a daily basis with the above plus a whole host of other things.

    • Brenda Finucane (NFXF Team Member)

      July 11, 2013 at 1:50 PM (Reply)

      Research into the many varied effects of fragile X premutations is relatively new. Just this year, the first international scientific conference on the fragile X premutation was held in Italy, and hopefully this was just the beginning of research interest into the ways that premutations affect carriers. Members of the fragile X community can help move research along by participating in research studies, donating to the NFXF, increasing awareness, and staying up to date on scientific breakthroughs in our knowledge about fragile X and related disorders.

  • I recently found out that I fall in the “gray area” for fragile x, while being tested prior to infertility treatments. I originally declined such testing but it was done anyway…I was furious when I found out. Moving on, I already have a 5 year old son and was told HIS children may be born with fragile x. Is this true? Also, should I share this info with my siblings, assuming they may also have this gene?

    • Brenda Finucane (NFXF Team Member)

      August 28, 2013 at 4:54 AM (Reply)

      Because of the connection between fragile X premutations and ovarian dysfunction, it is not uncommon for fragile X DNA testing to be offered to women undergoing fertility evaluations. While most do not have a fragile X mutation, some find out they are carriers, while others have results in the “gray zone” (also known as “intermediate alleles”). Fragile X intermediate alleles have anywhere from 45 to 54 repeats. Women with intermediate alleles are not considered fragile X “carriers”, and repeat numbers within this range are not at risk for expanding into full mutations in the next generation. Many intermediate alleles remain stable (i.e., don’t expand) when passed down in a family. However, in some people, having an intermediate allele may be a clue that the fragile X gene is unstable in a family; as such, there could be other family members with even larger expansions that fall into the premutation range. For this reason, genetic counseling is recommended to evaluate the family tree in the context of the intermediate result. Follow-up genetic testing that looks at the number of AGG repeats in people with intermediate alleles can provide additional information about the chance of expansion to a premutation. A genetic counselor may also identify other people in the family tree for whom fragile X DNA testing is indicated. To locate a genetic counselor in your area, go to the “find a genetic counselor” link at (Nat’l Association of Genetic Counselors).

  • Our family fit into the above, with all of us being tested after my niece had two of her three children identified as full mutation, my sister and my niece being identified as premutation(is this is the same thing as being a carrier?). I have been tested but am not a ‘carrier” and am childless. But the important question for me is informing other family members, as our parents have died, without giving us viable clues. Can a premutation father pass premutation onto his son? I guess not, but I need to be sure before contacting that branch of our family. I guess if by chance his wife was a carrier as well,……

    • I think I just found an answer to my question from Brenda Finucane above and am very grateful because I will now not stress this branch of my family but will concentrate on those who need me.

  • Thanks for this. I was looking for a quick, simple explanation of a carrier that included how it could be variable, when sharing informatin with the public.

  • The fragile x syndrome ruins in my family. My mother and her two sisters were the carriers since each had fragile x children . For years growing up ,I wondered what was wrong with my family. It was not until my daughter got pregnant and I started reading articles that I understand it better.
    When my daughter got pregnant 16 years ago ,she had two test done on her which one was the southern blot. They said she was not a carrier but since I have been reading articles they say a female carrier can go through menopause early which she just found out and she is 43 years old. So I was wondering if they could have missed diagnosed her or if I am just jumping to conclusions. She was tested in 1996. I can not bring this up to her because this is a touchy subject with her and her husband. I was never tested and she was my only child. I am 66 years old and really do not care about being tested at my age.
    Some how I have lost the test to see what the repeats were but the test did say and doctor said she was not a carrier. As a mother ,I am wondering what caused her early menopause . I had a hysterectomy so I can not say I went through it early.
    Thanks for your help!

  • My girlfriend and I knew she had some genetic disorder. She was tested at a fertility clinic and the results say “Universal Plus w/o MTHFR Deficiency Panel with Fragile X Syndrome-Positive Hereditary Thymine-Uraciluria (reproductive risk 1 in 400 / inheritance: Autosomal Recessive) I do not suffer from Fragile X syndrome. We are concerned about what this would do to any children we have. If I am understanding the article, they would have a greater risk (especially a male) of having a mental disability? BTW, she does have an autistic child from a previous marriage. Her first husband was never tested for any disorders.

  • My fiancé’s immediate family has a history of Fragile X. His older brother and his younger brother both have Fragile X as his mother was a carrier. My fiancé does not have it though but I understand he still carries the genes that can affect this disease??
    I am looking for some information as we are in the midst of family planning (and planning our futures together) however this does scare me and I would like to get some more information on how this may affect us and our kids.
    Even though he does not have fragile x, can he pass this on to our kids?

  • Hi Brenda! Its Pam Schwartz- Scott’s sister:). I came across this article and ironically saw you are the author. I would love to reconnect with you regarding some autoimmune disease issues I have and if there is a connection with Fragile X. My body produces mass amounts of scar tissue and higher than normal igg levels. Please let me know if you have any reaearch on siblings of fragile x or children of fragile x carriers, regardless if the child is a carrier of fragile x. I strongly believe the autoimmune diseases i have suffered from throughout my life and excess scar tissue coincide with fragile x running in my mom and her mom. Both also had autoimmune diseases. I am
    Not a carrier but do have their exact genetic makeup. Any advice would
    Be great.
    Warm Regards-

    Pam Schwartz- Roaenberg

  • I have 2 sons who have fragile x it wasnt until years after my son was born that I found out I have fragilx and that Im not just a carrier Im affected by it also

  • I am 75 years old. Have 2 sons with fragile X and have recently developed a tremor in my hands, neck and shoulders. Is this fragile x related, and can it be treated? Thank you

  • I know that I must have a fragile x premutation because my daughter who wishes to have children through natural childbirth has been genetically tested and determined to have fragile x premutation. Her Mom’s family has no fragile x history; in my family, several of my first cousins have children with the total fragile x syndrome. My question is: what is the probability that she could have a boy with premutation, a boy with total fragile x syndrome and is there any difference if the child was a girl instead of boy? Is there any way to tell the severity of the fragile x in a newborn before birth; my daughter currently does not exhibit any premutation symptoms but she is only 30 years old. Any advice/thoughts would be helpful. Thank you

  • I am a 75 year old female and have 2 sons with fragile x. I have recently developed a tremor in my hands, shoulder and neck. Is this due to being a carrier of fragile X? and is there some treatment available. Please let me know I would very much appreciate it. I live in Maryland.

  • Interesting

  • i need info on fragile x is their any kind of brain med. that can be given to a pt with this?

  • Hello,
    I was looking for some answers to a few questions and would be so happy if I could get them from you since you are very informed on this topic. I am getting ready to get married and we want children soon ….. My soon to be husbands mother and maternal aunt both have boys with fragile x …… I was wondering what likelihood we are to have a baby effected by it. Thank you in advance I would love love some feed back as it’s somewhat hard to understand these blogs about it.

    • Brittany,
      Your soon-to-be husband can be tested to see if he has the premutation. If he does, then you should seek genetic counseling. Please email me if you have additional questions –

  • What is the cross over point from carrier to FM? My daughter is 257 and we were told this is FM, based on this we were sent to a fertility specialist. She is only 21 and not showing any signs of menopase yet. Her fertility count is down to only half that of the average 30 year old already though. Should we be looking for another cause for this??

  • Brenda Finucane, MS, LGC

    July 13, 2015 at 5:31 PM (Reply)

    Hello Tracey,
    At 257 repeats, your daughter’s result is well within the range for a full mutation. As such, we would not expect her to be at risk for FXPOI or other fragile X-related premutation disorders. I’m not clear what is meant by a low “fertility count.” If your daughter has concerns about future fertility issues, she should consult a reproductive endocrinologist, gynecologist, or other specialist for further evaluation. This is recommended based on her history of a low “fertility count,” and not because of her fragile X full mutation.
    Brenda Finucane, MS, LGC
    Licensed Genetic Counselor
    Consultant, NFXF

  • My wife was diagnosed nearly 20 years ago as carrier of the Fragile X gene. It was discovered after she was tested following the learning that her sister’s two infant sons were born with Fragile X. We do not have any children, however we were wondering if there could be any side effects / symptom manifestations for her that would be due to her being a carrier. She is 59 years old and has been experiencing mobility problems in her lower extremities that have not been able to be exactly diagnosed yet. She also has been experiencing some thought process issues.
    Please advise… thanks!

  • My partners father has fragile X but she has been tested and doesn’t have it, is it possible to miss a daughter like that? She now wonders if the person she has called dad for 36 years actually is her dad.

  • Hello,

    At 40 repeats, I’m right at the border between having a normal allele and a grey zone one. Despite this relatively low number, I have many features common to premutation carriers: premature ovarian failure, ADHD, anxiety, obsessive thinking tendencies, and hyperflexibility of the finger joints.

    I’ve read that new research shows lack of AGG interrupts can affect both phenotypic expression and the likelihood of expansion in subsequent generations. Could this be the issue? This is of special concern to me, as I’ve managed to become pregnant naturally, and my baby is male. Considering I’m so severely affected despite having one normal allele, I’m worried about what to expect for my child if he inherits the abnormal one. Further, I know of a study that found gray zone alleles (albeit in the 51-60 range) were more likely to be passed on. Is my child at serious risk for complications like behavioral issues, learning disabilities, or autism? Is it possible my symptoms are just a coincidence?

    Thanks so much for your time.

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