Talk:Fragile X syndrome

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Contents 1 Incidence rates 2 common cause of autism 3 Martin-Bell merge 4 Fragility 5 Chromosomal Abnormality 6 question???? 7 Symptoms of MR reversed in mice 8 Benoit tragedy 9 Cyclic AMP Defect in Fragile X Brain 10 inappropriate tone 11 Removal of XlinkRecessive.jpg diagram from article

[edit] Incidence rates

I am no expert in the field, but I find the statistics kaleb"approximately 1 in 1500 males and 1 in 3000 females" strange. I mean, a female needs to have both chromosoms X with the defect in order to be infected. If the probability is 1/1500 for males, it would be 1/(1500*1500) for females (unless her parents are related, which should be rare). Or do we also count carrier females as infected? But in this case, the probability for women would be about 2/1500. --Bernard Helmstetter 21:47, 28 Dec 2004 (UTC)

Hi, I'm Kerrie and my entire family is affected by Fragile X -- one of my sisters and I are carriers and our children are affected: She has 3 adult children; her eldest son and daughter are seriously affected and her second son is fully autistic. I have two daughters, my eldest was not affected and my youngest is fully involved, meaning she's seriously developmentally delayed with some autistic tendencies. Anyway, the reason I'm pitching in here is because the former writer was incorrect when he wrote, "... a female needs to have both chromosomes X with the defect in order to be infected. First, no she doesn't: ONLY ONE affected X can and will cause symptoms from mild to severe, depending on the number of CGG repeats attached to that X. And please be sensitive with your choice of terminology: infected suggest an outside cause has infiltrated and infected the body, while this syndrome is genetic... you're either born with it or you're not. You can't catch it like some infectious disease. "Affected" is a better choice. Thanks. 76.102.191.124 (talk) 05:38, 24 March 2008 (UTC)Kerrie, 3/23/08, Novato, CA

I am not an expert, but I am a carrier and I am also the mother of a son with the full Fragile X mutation. The statistics are correct. First, there is a difference in the term AFFECTED, which the article refers to and INFECTED, which you reference above. It is complex and I could not begin to rebut your comments, but if you are truly interested in learning more, see the links that I added to the web site. They can and do explain how statistically this is not only possible, but a reality. Welcome to my world!--216.190.180.240 04:05, 26 Jan 2005 (UTC)

The figures as originally stated seemed to refer to the prevalence of the syndrome rather than the prevalence of the mutation that causes the disease, which, as Bernard points out, didn't make sense, as it's X-linked. I think it's accurate now. - Nunh-huh 04:18, 26 Jan 2005 (UTC)

The incidence rates for the disease have changed over time because of the test that is used. Originally, a person was identified as having the mutation by karyotyping. This method is much less sensitive than current PCR tests. Current tests can also distinguish between people who have a full-mutation (affected) and a pre-mutation (not affected, but pre-mutation syndromes like premature ovarian failure in women and ataxia/tremor in men are now being identified). Because the mutation is on the X chromosome, males are twice as likely as females to be affected. That being said, issues of X-inactivation and the dominant/recessive nature of the mutation make the prevalance in females a complicated subject. In any case, the incidence rates refer to the prevalance of the syndrome, which in most cases nowadays correlates well with the presence of the full mutation.

[edit] common cause of autism

Regarding the question if Fragile X and Autism are connected: YES! Several studies by the M.I.N.D. Institute in Davis, CA show a connection and they believe that Fragile X is one of the LEADING undiagnosed causes of Autism. Thanks, Kerrie, Novato, CA, 3/23/08

I think current research says no:

Klauck, S., Munstermann, E., Bieber-Martig, B., Ruhl, D., Lisch, S., Schmotzer, G., Poustka, A., Poustka, F. (1997) Molecukaleblar genetic acoryell nalysis of the FMR-1 gene in a large collection of autistic patients. Human Genetics, 100, 224-229.

Based on my own reaserch on the subject I found hthat there is no connection with Autism except that in 15%-20% of the children can display autism like symptoms Fragile X and Autism

There is a connection between Autism and Fragile X. The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) defines Autistic spectrum disorders (ASD) by a list of clinical criteria. All children with Fragile X meet this criteria. In addition approximately 15% to 20% meet the full criteria for Autism, making Fragile X the leading genetic cause of of autism. In addition, there is a relationship between FMRP (the protein absent in Fragile X) and autistic behavior: low levels of FMRP are associated with higher mean levels of autistic behavior as measured by the Childhood Autism Rating Scale (CARS). As clinicians have begun to use the genetic test for Fragile X amongst their autistic patients, they have begun to separate out known causes of autism, like fragile X and others, from the larger pool of autism (of unknown cause); separating the disease by cause instead of by clincal features has lead to confusion. In the end there are likely to be hundreds of genetic causes of autism (including the currently known ones), but how all of these mutations lead to the same disease is yet to be discovered.

Trottier, G., Srivastava, L. & Walker, C. D. Etiology of infantile autism: a review of recent advances in genetic and neurobiological research. J Psychiatry Neurosci 24, 103-15 (1999).

Hatton DD, Sideris J, Skinner M, Mankowski J, Bailey DB Jr, Roberts J, Mirrett P. Autistic behavior in children with fragile X syndrome: Prevalence, stability, and the impact of FMRP. Am J Med Genet A. 2006 May 12

[edit] Martin-Bell merge

As far as I can tell, Martin-Bell syndrome is just another name for Fragile X syndrome, so I would assume the articles should be merged.

http://www.emedicine.com/ped/topic800.htm http://www.autism.org/fragilex.html 65.66.86.67 15:16, 21 February 2006 (UTC)

I second the motion for merger with Martin-Bell syndrome based on the article Fragile X

I agree, Martin-Bell is another name for Fragile-X. See http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=309550/ Xanin 12:13, 25 April 2006 (UTC)

Fragile X is the same thing as Martin-Bell syndrome. A brief history: 1943: Martin and Bell described the first pedigree of inherited mental retardation 1965: The first “fragile site” on a chromosome is discovered (Debakin). 1968: Fragile sites were shown to be inherited chromosomal features (Lejeune et al.) 1969: X-linked inheritance pattern is recognized as the cause for male preponderance in mentally retarded population (Lehrke, 1969) 1960- 1980’s: Fragile site on X chromosome is linked to X-linked mental retardation, syndromic nature of disease is established, and the current clinical picture was formulated; named the Martin-Bell syndrome after the first pedigree (Lubs, 1969; Richards and Webb, 1982) 1991: The mutation leading to FXS is identified, the gene isolated;"Martin-Bell syndrome" is replaced by "Fragile X syndrome" in the scientific nomenclature.(Verkirk, et al., 1991)

I merged them, and will work more on the article. NCurse _work 08:50, 22 October 2006 (UTC)

[edit] Fragility

The mutation doesn't actually make the X chromosome fragile or more likely to break into two, does it? John Riemann Soong 23:32, 20 August 2006 (UTC)

No, fragile refers to a constriction followed by a thin strand of genetic material seen on karyotyping, giving it a fragile appearance. I have never heard of it actually being actually more fragile. --WS 23:42, 20 August 2006 (UTC)

[edit] Chromosomal Abnormality

Recently, someone added a category that Fragile-X is a chromosomal abnormality. Several things can be said about Fragile-X.

1. It is classified in ICD as a chromosomal abnormality (Q99 -- Chromosomal abnormalities, not elsewhere classified).
2. It can be diagnosed using a karyotype test, which looks for an unusually formed X chromosome (hence the initial classification).
3. It is a single-gene effect, and modern tests no longer use the karyotype tests.

I don't believe that many human geneticist would currently classify Fragile-X as a chromosomal abnormality, if any would. It is no more a chromosomal abnormality than is, say, myotonic dystrophy or Huntington disease. On the other hand, it is verifiably misclassified as such by a reputable source. I'm inclined to delete the classification, as it is misleading, particularly to individuals who are coming to Fragile-X for the first time. Genetics411 21:30, 15 January 2007 (UTC)

It is also classified as a chromosome disorder by Medical Subject Headings, and that classification is updated every year. And it isn't as though the classification has been abandoned -- Ectodermal dysplasia was classified as a chromosomal disorder in 2006 but not in 2007, which strongly implies that Fragile X's continued inclusion in the category is due to a recent choice made by National Institutes of Health researchers, not due to inertia. --Arcadian 05:24, 20 January 2007 (UTC)

While you are correct that Fragile X, being a trinucleotide repeat disorder, is not caused by a translocation or aneuploidy, the syndrome and the visible karyotypic abnormality go hand in hand. Either way, I'd rather go with the ICD code even if it's a bit misleading. If the ICD classification is in dispute that's a matter to take up with them, not on wikipedia. Unless of course you can cite an external reference disputing the ICD classification... Robotsintrouble 14:24, 26 January 2007 (UTC)

[edit] question????

What is the life expectancy of a person with the Fragile X syndrome? —The preceding unsigned comment was added by 69.238.218.141 (talk) 01:57, 11 March 2007 (UTC).

One Mother's Opinion...

I'm a carrier of the Fragile X (FX) gene and a single mother of two adult daughters: my eldest (now 22 yrs. old,) was born without my affected X chromosome and is a very intelligent and dynamic young woman, while my youngest (now 21 yrs.,) was born with my affected X, and at age 12 was accurately diagnosed as having "Fragile X Syndrome with autistic tendencies." She currenly functions between a 5 - 10 year old level, depending on the situation. She reads at a second grade level and "doesn't do math," but she can use a calculator with help. She doesn't understand the denominations of money and can't tell time unless it's displayed on a digital clock. She does understand the days of the week, weeks of the month, and months of the year. Both my daughters have participated in studies with Stanford University and I've been researching and following the scientific progress of FX for almost 10 years. In addition, my sister who's two years older than me has three children, all of whom were born with FX; her youngest being fully autistic/non-verbal. (My eldest sister, four years older than me, wasn't a carrier and had two unaffected kids.)

So, four kids out of the seven that my two sisters and I've had have been born with FX and each one lives with a different level of the syndrome: from mild to severe (autism.) You could say my perspective is from the field of day-to-day living with first-hand experience of how this condition shapes the lives of your children, (affected and unaffected,) your immediate and extended family, your marriage, your relationships with others, and in turn, every aspect of your own life. It's been quite a journey! As with all great things in life, there are blessings and challenges... but the difficulties will lead way to positive outcomes, if you're open to humble teachings!

From my understanding, Fragile X doesn't necessarily shorten one's lifespan. Out of all the physical abnormalities associated with Fragile X, none involve vital organs... except the brain!** (Feel free to correct me if I'm wrong!) Each individual, depending on the number of "CGG" repeats within their X chromosome, will exhibit various physical traits, which may include: "hypotonia" (low muscle tone,); an "absence of muscle mass" (don't know the scientific term for that,); "connective tissue dysplasia" (weak tendons and ligaments that cause very loose joints,); pronated ankles sometimes severe enough to cause foot deformites; "scoliosis" (crooked spine,); narrow faces; longer or larger ears; narrow palates (roof of mouth is very narrow and can cause speech problems as well as crowded teeth,); and course, wirey hair... to name a few.

My daughter's hypotonia and lack of muscle mass causes her metabolism to be slower, so she easily gains weight. She also tires easily and is prone to heatstrokes, which I sometimes forget and have to abort a summer hike halfway out! To keep her strong, she works out twice a week at the YMCA with a 1:1 aide, and a few times a week we do other activites like take nature walks, (she LOVES nature!) swimming, (she LOVES the water but only up to her chest!) and Tai Bo (LOVES her Billy Blanks videos!) I believe keeping her active is a huge factor in keeping her healthy and strong... and that will only gain importance as she ages.

• • **Regarding the brain, studies show that with early and ongoing intervention of appropriate therapies and supports such as Speech and Language, Occupational Therapy, Adaptive PE, and assigning a 1:1 Aide in the classroom, an affected person's IQ can and does increase over time! (My youngest is showing more intelligence and an ability to adapt to adult life in so many ways! My only regret is that NOW she's ready for 3rd, 4th and 5th grade, but those opportunities are in the past. Still, I'm working on other ways to provide education for her.)

There are also a miriad of hyper-sensitivities that are triggered by daily stimuli: Loud noises or annoying sounds can send them through the roof; bright lights bother their eyes and can cause them to feel highly irritable; direct eye contact with others is unnerving and difficult to maintain; their sense of smell is amazingly acute; light touches on the skin can feel like an assault; loose clothing that causes friction on the skin isn't easily tolerated (hello Spandex!) and keeping hair short or tied back to avoid stimulus on the body is also common.

Energetically speaking, people with FX are EXTREMELY sensitive to energies from all sources: people, animals, music, plants, weather, geographical locations, dreams, etc. Other people's words, body language, aura, vibes, etc., will easily penetrate their personal boundaries, unless they're aware of how to protect their personal space. This overall sensitivity makes them great artists and intuits. They FEEL your soul's force, so they're excellent at identifying who's pure of heart and who has ulterior motives. In general, I see they're more in tune with the Life Force that flows through all of us because they don't understand the generally accepted belief that we're seperate from one another. (Recent discoveries in the field of Quantum Physics proves that we ARE all connected -- that energetically there is no separation between atoms and molecules in all things, so who's the retard? lol!)

Which brings me to the JOY factor! It's very important to note that people with FX are generally more joyful than the average person, probably because they don't have a developed ego to spoil their fun! While they beam over personal accomplishments, they aren't focused on performing better than the next guy (unless they're in Special Olympics!) -- they'd rather work side-by-side and get along with others than triumph over them. They also LOVE their family: as proof, a few years ago TIME magazine did a cover article on how an autistic person's brain responds to seeing a loved one walk in the room, and they LIGHT UP! In my experience, family, love, and laughter are the MOST important things in the life of a person with FX... so it begs to be repeated... who's the dummy here?! If more of us were like these brilliant souls, I believe there'd be Peace On Earth.

Yes, we have lots of great scientific research, endless studies and educated guesses pertaining to Fragile X Syndrome and all the questions that go along with it. It's all good information to help us understand the physical aspects, (very useful in obtaining services and supports, too!) However, to me, as a carrier and mother of a child with FX, the physical facts aren't the Final Word. I feel the spiritual aspect is ulitmately the highest court, (spiritual, not religious!) If I may, I'm going to share my experience and understanding of this baffling miracle of life we're all a part of, and it goes something like this: Before we are born as human beings, we're simply souls, without a physical body. Our own Divine Intelligence (or soul, essence, etc.,) chooses to come into this world to gain greater awareness (or consciousness,) so that we will be further awakened unto our TRUE nature, which is that we are all faces of God -- Great Spirit, Jehova, Allah, Creator of All Things, Unlimited Universe, -- whatever label you like. We choose the body we inhabit to teach ourselves and others; we choose the family we're born into to teach ourselves and others; we choose everything that "happens to us" to teach ourselves and others. And one of the most basic, yet greatest lessons we're all here to learn is what people with Fragile X Syndrome and other special needs already know: to slow down, relax and enjoy what really matters in life... LOVE!

So, that's my sermon on the keyboard tonight. Thanks for tuning in! --BrightWahine (talk) 11:49, 11 January 2008 (UTC)BrightWahine--BrightWahine (talk) 11:49, 11 January 2008 (UTC)

—Preceding unsigned comment added by 76.102.191.124 (talk) 11:37, 11 January 2008 (UTC)

[edit] Symptoms of MR reversed in mice

"Researchers at the Picower Institute for Learning and Memory at MIT have, for the first time, reversed symptoms of mental retardation and autism in mice." [1] Brian Pearson 03:53, 26 June 2007 (UTC)

I tried to include it, but didn't want to write more about it. Thanks for the link! NCurse _work 19:42, 26 June 2007 (UTC)

[edit] Benoit tragedy

It is suspected that Chris Benoit's son had Fragile X, and this may have played a part in the tragedy. Should this be mentioned in the article?--Bedford 02:26, 29 June 2007 (UTC)

Where is it "suggested"? If you can provide a reference please add it, otherwise it seems like mere speculation. (Citation tag placed) ABVS1936 05:43, 30 June 2007 (UTC)

[edit] Cyclic AMP Defect in Fragile X Brain

http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0000931 Kelley DJ, Davidson RJ, Elliott JL, Lahvis GP, Yin JCP, et al. (2007) The Cyclic AMP Cascade Is Altered in the Fragile X Nervous System. PLoS ONE 2(9): e931. doi:10.1371/journal.pone.0000931

This paper could be added to the References section and was published using the Creative Commons License http://www.plosone.org/static/license.action

The following could be added to the current research section: At the University of Wisconsin-Madison Waisman Center, scientists identified that production of cyclic AMP, a signal transduction molecule, is reduced in fragile X brain. This alteration was consistent across fragile X fly, mouse, and human neural models. Rescue of the reduced cAMP production in the fragile X fly was possible by reintroducing the FMR1 gene.

Abe2mu (talk) 06:37, 23 November 2007 (UTC)

[edit] inappropriate tone

The following bit is familial-sounding (and vaguely sarcastic) and should be revised:

"The diagram (right) of X-linked recessive inheritance is not entirely inappropriate but it markedly oversimplifies the situation and does not provide a sufficient foundation for genetic counseling about the fragile X syndrome." 71.234.109.192 (talk) 04:39, 3 March 2008 (UTC)

I agree the tone is inappropriate. The sentence was added by an anon in late October 2005, and they do not appear to have made any edits since (someone else has used that IP since), so there's no point in asking them about it. I've revised the sentence to

The diagram (right) of X-linked recessive inheritance markedly oversimplifies the situation.

and I've left the following sentence (added since the anon made their edit) explaining why the diagram is oversimplified, although that sentence could be rewritten for a less technical audience.-gadfium 07:59, 3 March 2008 (UTC)

[edit] Removal of XlinkRecessive.jpg diagram from article

Given that inheritance of fragile X syndrome is complicated and an X-linked dominant condition, the diagram on the right is completely inappropriate. Not only does it make the disorder appear recessive, but it doesn't even begin to show the actual mode of inheritance. If there is no suitable diagram available, surely it is better to use none than to use such a misleading one? Unless there are any objections, I'll remove it within the next week. –79.74.96.98 (talk) 06:57, 27 May 2008 (UTC)