Talk:Rett syndrome

Factual inaccuracies

I'm the sister of a girl with Rett Syndrome, and I have to say this article is very worrying, as it appears to suggest in the first para that the gene is recessive, and can 'lie dormant for generations'. Then it goes on to say that the vast number of cases are due to 'random mutation', which is my understanding. In fact, I've had genetic testing at a centre specifically researching Rett Syndrome, and they confirmed this. It's not passed through families at all. Leaving this reference in is misleading and alarmist.

I think the first para, in fact, may come from some very early work, which has since been discounted.

The article also suggests 'marriage and work is possible' in later life. I've only ever met one Rett girl who had anything resembling a normal life, and she was diagnosed as 'several mentally retarded'. In fact she had mosaicism and wasn't affected by her RS. I believe this comment to be hugely misleading. My sister, for example, is 26, lives in a home, is in a wheelchair, can't communicate and has multiple physical problems.

I'll take a closer look at this article (I'd never read it!) because I'm not familiar with the full spectrum of the disease (most of what I see in the hospital conforms to your impressions) but am often suprised by what people with seemingly horrible diseases are capable of! InvictaHOG 03:01, 2 May 2006 (UTC)

I removed the X linked dominant picture as it suggests a Mendelian style of inheritance and may confuse some people. As the correction has been made, it is a de novo rather than an x dominant / recessive inheritance. —Preceding unsigned comment added by 172.201.204.108 (talk) 17:06, 4 November 2007 (UTC)

Flagged for cleanup

Article is a grammatical and spelling nightmare and uses overly brief prose (almost entirely lacking articles like "the" and "a.")

Confusing paragraph

With the discovery of the MeCP2 gene deletion that is charactistic of Rett's Syndrome in 1999, the number of misdiagnosed girls and women has increased sharply. Many of the former beliefs about mental abilities, life span, and general health have significantly improved with the discovery of more cases.

Gene mutation, not deletion, right?

Why would discovering the role of MECP2 lead an increase in misdiagnosis? 203.34.41.43 00:41, 12 December 2005 (UTC)

A deletion is a type of mutation. On the second point, the article is somewhat ambiguous. Either it means to say that many females though to have had Rett Syndrome in fact have something else or else, many females thought to be normal in fact have Rett Syndrome. I believe the former is the real meaning. Theshibboleth 09:08, 19 December 2005 (UTC)

Helping clean up Rett syndrome

I asked someone who has reliable evidence (she has rett's herself - forme fruste) about the veracity/accuracy of this article.

She said there was a lot wrong with it. Not all girls lose speech or have seizures.

The regression is frequently a lot later than 18 months.

There is something about genes and some of them are silent.

Just a few of the interesting points she made. All or most supported by medical research.

--EuropracBHIT 06:42, 23 March 2006 (UTC).

While the symptoms may not apply to the case of the person you asked, I have personal experience with a case of Rett Syndrome in which the symptoms stated do apply. I think we need to be careful about what we remove, though there is no question that some of the information here is incorrect. I might be able to better source different parts of the article. Unfortunately, a lot of the information online about Rett Syndrome is also inaccurate. I even remember reading something online which said suggested that nothing beyond the clinical symptoms of the disorder was known. Theshibboleth 04:19, 25 May 2006 (UTC)

Dominant or recessive?

• "The gene is recessive and can therefore lie dormant for generations."
• "Rett syndrome (symbolized RTT) is X-linked dominant, affecting almost exclusively girls."

I find them so confusing. Which one is it, dominant or recessive? 70.20.159.28 18:17, 15 April 2006 (UTC)

• Good spotting. (Here's the diff that claimed that Rett is recessive). It's X-linked dominant (which is a bit different than autosomal dominant). See Sex linkage and Autosomal dominant. 203.34.41.43 08:21, 23 May 2006 (UTC)

I've added the Image:X-link_dominant_father.jpg but I'm not sure if it is entirely suitable as it shows "unaffected sons". --apers0n 06:14, 17 October 2006 (UTC)

And an "affected father" reaching reproductive age. 203.34.41.43 04:24, 25 October 2006 (UTC)

Gonads or Gametes?

"Unlike most genetic diseases, most individuals with Rett syndrome result from spontaneous mutations in one of the parent’s gonads. It has been argued that one cause of the majority of Rett syndrome individuals being female is that MECP2 mutations are more common in male gonads" - wouldn't gametes be better here? C0pernicus 14:42, 9 February 2007 (UTC)

hahaha, nice... yer, change it. KX36 15:50, 9 February 2007 (UTC)

maternal-paternal X-inactivation ratio

"In most cases,[citation needed] 50% of cells use the maternal X chromosome while the other 50% uses the paternal X chromosome."

I didn't write this, and i haven't got a citation (although what I am about to write is straight from my lecture notes as fact, so I assume it's well established). X-inactivation is known to happen at 15-16 days gestation (~5000 cells) and is a "random" choice according to the X-inactivation article. Statistically, that would mean the fraction from each parent would be normally distributed, with the average being 50:50. It is totally impossible to predict which cells, tissues and organs will retain which chromosome until much later if one of them is defective and pathology is seen. --KX36 16:08, 9 February 2007 (UTC)

Expand tag

I put the expand tag in the treatment section. I'm wondering if that section might benefit by being written in prose instead of a list. --Umalee 18:52, 15 February 2007 (UTC)

Genetics Section

The genetic section is mostly right, and from what I read on the talk page, a great improvement on how it used to be. It is correct that Rett syndrome is X-linked dominant, and the picture is correct for how Rett syndrome mutations would be inherited from an affected mother, however, this is not what is seen in practise. Most (there have been approximately 12 - 15 familial cases) people with Rett syndrome do not have children. The familial cases of inherited MECP2 mutations have been from people who would not be clinically defined as having Rett syndrome (they're often termed "unaffected carriers").

Would anyone object to including something along the lines of "In most cases, Rett syndrome is caused by de novo mutations of MECP2 and are hence not inherited from the parents" (with an appropriate reference) in the genetic section? AmiBebbington 03:51, 6 September 2007 (UTC)

Mouthing

What's mouthing (stereotypic, repetitive hand movements)? I couldn't find a definition anywhere. D021317c 16:10, 2 October 2007 (UTC)

My understanding is that mouthing is involuntarily putting their hands in their mouths. http://www.healthline.com/galecontent/rett-syndrome http://www.rettsyndrome.org.uk/_downloads/OT_Q3.pdf 216.226.176.142 19:28, 18 October 2007 (UTC)

Revision suggested, causes (x-chromosomal vs. mutation)

"Rett syndrome (symbolized RTT) is X-linked dominant -----!!!!!THIS IS NOT X-linked DOMINANT - NEEDS MODIFYING - IT IS A DE NOVO MUTATION!!!!!!----,"

Given that this is true, immediate revision is highly recommended; I have checked some literature, but due to my field of specialization it probably didn't include the cause. Apparently it is not almost exclusive, but completely exclusive to females however.

Further I would like to propose a title change to Rett's Disorder instead of Rett Syndrome.

(Nerusai, failed to login, as usual) 82.74.28.173 11:08, 1 November 2007 (UTC)

Hi Nerusai. I think part of the confusion is that people with Rett syndrome don't generally have children. If they did, the MecP2 mutation would be X-linked dominant. I agree, it is a de novo mutation in almost all cases (as reflected in the article). The few familial cases of Rett syndrome, however, were inherited in an X-linked dominant way.

Rett syndrome is not completely exclusive to females, though the presentation in males is different, and males with the MecP2 mutations commonly found in females with Rett syndrome are unusual.

I would reject the title change. Almost all websites and research articles call it Rett syndrome, and it is called this in the DSM and ICD.

Ami AmiBebbington 06:47, 7 November 2007 (UTC)

Added redirect from Rhett Syndrome

Rhett syndrome is another name for Rett syndrome, so I added that as a redirect. Killroy (talk) 19:49, 10 February 2008 (UTC)

"Rhett syndrome" is a mis-spelling of Rett syndrome, not another name for it. It is named after the person who first published about it, whose name was spelled "Rett". Still, good idea to add the redirect, people can get confused. AmiBebbington (talk) 02:41, 15 February 2008 (UTC)

Gender and Rett's syndrome section

I thought this section was missing a sensible explanation for the disparity between female and male cases of Rett's, and provided what I hope is a good explanation of why. I also provided a source, from the primary literature, that agreed with my argument.

The second paragraph, however, I found to be somewhat confusing and contradictory. There was a weasel-word sentence I removed, saying "Additional scientific studies have disproved this" with no source.. and, the source that was given for the "alternative theory" (which really is just another way to state the above paragraph, but in clinical rather than biological terms) was from a journalistic article, which *can* be viable sources, but in any scientific article, the primary literature is the only truly reliable source.

So, I stopped short of deleting the 2nd paragraph, but, I'm not really sure what it adds. The paragraph I wrote could be integrated with it, perhaps. In any case, this is my first non-minor contribution so, I hope it's taken constructively. Mr0t1633 (talk) 04:58, 20 April 2008 (UTC)

Your first paragraph is an excellent contribution. I changed a bit of the wording, because although people with Rett syndrome technically are "mutants" this is not a term that is generally used to describe people with genetic mutations. I added a bit more information about males and Rett syndrome, with references, and tidied up some of the sentence structure around "MECP2 mutations". The mutations are mutations of the gene MECP2, and there are many different ones (more than 200 have been described), so it isn't quite accurate to say that people with Rett syndrome are affected by "the MECP2 mutation". Hopefully adding the primary reference to the fact that some (46XY) males have indeed been born with mutations of MECP2 that are associated with Rett syndrome in females, which discounts the idea of universal lethality to 46XY fetuses, has cleared this up. The main issue is that male neonates with possible Rett syndrome present with such different symptoms (neonatal encephalopathy) to females with Rett syndrome that the genetic test for a mutation of MECP2 isn't suggested. The true incidence of this is therefore extremely difficult to ascertain. AmiBebbington (talk) 06:59, 24 April 2008 (UTC)

Thanks, I'm glad to contribute. Also, good job on cleaning up the mutation wording; it's important to be consistent so those who don't necessarily know the difference between, say, an allele and a gene can understand and be free of confusion. Hell, I have a degree in biology and I get confused sometimes, heh. But yeah, referring to "the MECP2 mutation" implies MECP2 is a mutation, so to be accurate one would refer to a "mutation in the MECP2 gene" (although I prefer 'locus'). Interesting point regarding the failure to diagnose Rett's in males, due to both the notion that it only affects females, and the symptoms as you describe. Again, thanks for the feedback and for helping to clean up the article! Mr0t1633 (talk) 13:44, 20 May 2008 (UTC)

Revisiting Mode of Inheritance

I'm afraid the decision to leave out the MECP2 mutation's mode of inheritance is a confusion by people misunderstanding the term "X-linked dominant mode of inheritance". The MECP2 mutation's mode of inheritance is indeed X-linked dominant, though in 99% of cases, the mutation is sporadic. It is sporadic because in most cases, Rett patients do not have children. However, if a Rett patient were to have a child and passed on her X-chromosome bearing the MECP2 mutation, the child would also have Rett syndrome. So, although it is usually a sporadic or de novo mutation, its mode of inheritance is still X-linked dominant. Also, there are familial studies of the syndrome, though rare, that confirm this. Therefore, I propose to put this information back in the article, albeit with clear explanation in order to avoid confusion for the laymen (this isn't a technical genetics article, after all!). If there are no arguments against it, I will go ahead and change this in a few days.Mjatucla (talk) 04:51, 19 August 2008 (UTC)

Regarding Gene Therapy for Rett Syndrome

There is a misleading statement in this article here:

Currently there is no cure for Rett syndrome, although there has been some promising results with gene therapy in mice.

It references [this article] from BBC (which isn't a reliable source). The ultimate source for that study is [Guy et al., 2007], and in that study, the Mecp2 gene was repaired by manipulating the gene in a transgenic mouse that had the gene disrupted in order to restore functional Mecp2. Upon restoration of Mecp2 gene function, the Rett syndrome phenotypes disappeared in the mice. This is, however, quite different from gene therapy. What it does tell us is that restoring MECP2 gene function to what it is in non-Rett individuals is likely to eliminate Rett syndrome in Rett patients. I would reword that statement to say:

Currently there is no cure for Rett syndrome, but it has been shown that restoring MECP2 gene function may be the path to a cure.

I know it might seem like silly semantics, but that's what we're here for, right? :) If there's no argument, I will change this in a few days.Mjatucla (talk) 04:51, 19 August 2008 (UTC)