Talk:Spinal muscular atrophy

Wiki Education Foundation-supported course assignment
This article is or was the subject of a Wiki Education Foundation-supported course assignment. Further details are available on the course page. Student editor(s): Anderclamusc. Peer reviewers: Averstumor.

Above undated message substituted from Template:Dashboard.wikiedu.org assignment by PrimeBOT (talk) 10:00, 17 January 2022 (UTC)

Merge from other articles
I suggest relevant sections of the Spinal muscular atrophies article are merged into this article. It appears that whilst the said article was originally written to contain general information on muscular atrophies, it was expanded by subsequent editors with information related strictly to SMA; this information should be merged here IMHO.

Further, I see little point of having Spinal muscular atrophy type 2 as a separate article while most of its content is covered here. Suggested merging the relevant sections of the other article into this one. kashmiri (talk) 01:48, 18 December 2011 (UTC)
 * I could not disagree more with Kashmiri SMA phenotypes are actually different diseases in the way the condition manifests in the body. Each type should have their own pages. Just as Leukemia should have it's own page and not just merged into a cancer page. — Preceding unsigned comment added by 108.46.139.65 (talk) 15:32, 24 December 2011 (UTC)


 * Thanks for your response. SMA types are not different diseases but different forms (phenotypes) of the same condition - I hope this is very clear from reading the Causes section. If you really want to use comparisons, this would be like light myopia, medium myopia and high myopia: I hope you don't insists these three types of myopia each deserve a separate article. Moreover, you can't really find medical literature from the fields of molecular research, genetics and pharmacology that would deal with only one SMA type except for care-related works (searching relevant databases is encouraged). In short, I do insist that spinal muscular atrophy type 2 is deleted as it brings nothing new atop of spinal muscular atrophy. kashmiri (talk) 00:31, 25 December 2011 (UTC)

Section "Causes" requested to be edited
The part of "Causes" section that deals with genetics is a mess and includes factually incorrect information. Someone please rework it. kashmiri (talk) 01:50, 18 December 2011 (UTC)
 * Done. Text revised. kashmiri (talk) 00:16, 19 December 2011 (UTC)

The graphic that accompanies the "Causes" section is incorrect. Autosomal recessive inheritance results in offspring with a 1:2:1 (affected:carrier:unaffected) ratio, without sex linkage. This graphic shows only female offspring being affected. Actually 25% of male offspring would be affected as well. — Preceding unsigned comment added by 71.67.97.128 (talk) 08:39, 2 January 2013 (UTC)
 * Big thanks for pointing out. I will correct the picture in the first available moment.  kashmiri 12:07, 3 January 2013 (UTC)

Gene therapy
Some IP user keeps replacing the Gene therapy entry under "Therapies" with own edits which, unfortunately, I have been forced to revert twice. The IP author's text is as follows, and the reasons of my reverts are given beneath.


 *  AAV9 Systemic Delivery of SMN1: Pre-clinical data in the severe Delta 7 SMA mouse model has shown the greatest increase in survival to date (400 day extension in life as opposed to the typical 15 day survival in the severe mouse model). In addition this program has tested efficacy and safety in non-human primates. Systemic delivery of AAV9 has proven to be efficacious and safe in pre-clinical studies as a potential therapy for Spinal Muscular Atrophy.

Barring a somewhat clumsy writing style, the second and third sentences are misleading and, as a matter of fact, factually incorrect because there has been no studies whatsoever on humans (even less on SMA patients) of safety and efficacy of AAV9 systemic delivery. Additionally, there has been only one study of AAV9 delivery in non-human primates which tested AAV9 safety but not SMN1 replacement efficacy (as these were ordinary, "healthy" macaques, not SMA animal models). There has been not a single study of SMN1 delivery using AAV9 viral vector even in large animal models, least in SMA patients.

Further, the first reference is unrelated to the topics - the quoted article actually discusses effectiveness of a novel AAV9 delivery method (intravascular injection). The second reference was indeed retained in my text as it was useful, although referenced directly to the source material using the format.

I also do not clearly understand why gene therapy, which is a very technical term (wikilinked in my text), is replaced by the said IP author with ambiguous "AAV9 Systemi Delivery of SMN1".

Whilst it is very ok to be enthusiastic about one particular therapeutic approach to SMA, I strongly suggest that any edits here are done after thorough research and with correct references. The article has had a nearly empty "Therapies" section for many years, with hardly anybody contributing a word to it - until I expanded it just a few days ago, after a lot of research work. It is saddening that the section instantly gets cluttered with well-intentioned but imprecise, confusing and poorly referenced edits.

Also, a correct use of the and, whenever possible,  templates will be greatly appreciated.

Finally, whilst anonymous IP edits are not forbidden, it is considered a good style to edit Wikipedia from a registered account, especially when doing reverts. Thank you.

kashmiri (talk) 16:48, 26 December 2011 (UTC)

Prosensa no longer working on SMA treatment compound

 * An unclear mechanism of action is found in the following compounds currently under research:
 * PRO105 — a proprietary compound under development by Prosensa BV, The Netherlands

This is no longer the case. Prosensa have stopped development on this compound. Can someone remove the reference to it? Thanks! --Henry A Stanley (talk) 13:40, 12 April 2012 (UTC)


 * If there are no objections, I'll do it myself. --Henry A Stanley (talk) 08:29, 13 April 2012 (UTC)


 * Thanks :) kashmiri (talk) 12:53, 2 May 2012 (UTC)

Further clean-up required
Back in December 2011, I managed to give quite a decent shape to the article. Still,as of today (May 2012), I see a need of further clean-up: kashmiri (talk) 15:01, 12 May 2012 (UTC)
 * Introduction needs rewriting in a non-technical language;
 * Types needs to be improved: 5-type classification presented more clearly (including type 0 and sub-types Ia/Ib, IIIa/IIIb), references need to be added (including reference to the original classification); the 18 months barrier separating types II and III needs to be presented in a less rigid way (in order to accommodate those researchers who propose lowering it to around 12 months; or even base the entire classification solely on the functional status);
 * Causes needs further references to sources; also, explanation is needed why low levels of SMN damages motor neurons so selectively, along with proposed mechanism; the entire cellular process of the disease can also be presented as stages (to be matched by therapeutic targets to be identified in the Emerging therapies sub-section);
 * Symptoms has been essentially copied from an old version of the article and might need revising; could be linked to or even merged with the Types section;
 * Diagnosis needs more info on carrier screening and pre-natal screening, including issues of recommendations and research on cost-effectiveness (which has to be presented as a country-specific estimate);
 * Therapies should be shortened. Palliative care needs reworking and slight expansion (maybe also renaming to "Supportive care"?). For Emerging therapies, ideas may include: separating therapeutic pathways that are currently pursued from those which have been proved futile and those yet to be researched; re-arranging therapeutic methods more in line with the therapeutic target; cleaning-up the source list (moving some to a new Further reading section?). A word on the SMA Treatment Acceleration Act might also be useful for U.S. readers.
 * Prognosis should be merged with Types IMHO.

Life expectancy
Life expectancy data are based on 1990s studies and as of the 2nd decade of 21st century they are gravely out of date, with life expectancy in SMA significantly higher:

"'Late last year [in 1997], Petra Kaufmann and Darryl De Vivo, co-directors of the MDA Clinic at Columbia University in New York, were part of a research team that found that children born with type 1 SMA between 1995 and 2006 lived significantly longer than those born between 1980 and 1994. Nowadays [in 2008], 74 percent of children with type 1 SMA live to age 2, as compared to only 31 percent of those born before 1995. This tremendous improvement is due in large part to better supportive care, particularly the use of assisted ventilation, cough assist devices and feeding tubes. But, say the researchers, this also reflects a change in attitude toward aggressive treatment for children with severe SMA. Thanks to SMA research advances, there is more optimism about future treatment possibilities for those affected by this difficult disease.'"

Same with regard to other SMA types.  kashmiri 14:30, 3 March 2013 (UTC)

Routine screening
Re. your edits, even if the source says so, neonatal screening cannot be offered to "couples" - it can only be offered to neonates (including children of single mothers). We need to ensure sanity of the article.

The entire section needs reworking anyway because since 2009, when the source paper was written, both the genetic test costs have come down significantly (to just a few USD per test) and an approved therapy has come to existence. I will try to rework the paragraph. I am fairly well aware of the ongoing discussions in the medical and regulatory community on the matter, although not yet sure whether more recent published sources exists. If you had some, thanks for linking or adding to article. — kashmiri  TALK  16:29, 26 December 2016 (UTC)

One does not own the Talk page
Kashmiri, I sense that you have a proprietary relationship with this page, which is not uncommon among WP editors. However, this ownership is not encouraged on WP, and, further, does not extend to the Talk page of "your" article. It is exceptionally bad form to excise another editor's Talk page submission, no matter how abusive, or no matter how hare-brained you may find it. True, WP isn't a guide. The Talk page is not part of WP the encyclopedia. Nobody expects to go to the Talk page for additional reading on the topic of a WP article. You really should revert your recent reversion on this page if you intend to play by the rules.--Quisqualis (talk) 20:40, 26 December 2016 (UTC)
 * Removed as "harmful post" per WP:TPO - seems the editor's sole purpose of registering on Wikipedia was to provide this pseudo-medical advice (an extremely harmful one on top of it). Moreover, reverting will delete your post above - catch 22. You should have posted it on my Talk page - comments on an editor's behaviour do not belong to mainspace anyway. — kashmiri  TALK  22:45, 26 December 2016 (UTC)

unsourced
this is unsourced and generally not a section we have per MEDMOS

'In popular culture


 * 39 Pounds of Love is a documentary film written and directed by Dani Menkin and starring Ami Ankilewitz, an Israeli 3D animator who lived with spinal muscular atrophy.
 * "97 Seconds", the third episode of the fourth season of House, features a man with spinal muscular atrophy who develops symptoms that could be related to his SMA or something else.
 * Laughing At My Nightmare is an autobiography written by Shane Burcaw, focusing on his medical and social life. He suffers from SMA2.

-- Jytdog (talk) 20:51, 5 April 2017 (UTC)


 * There can be a section titled "Society and culture" per WP:MEDORDER. That said, the "97 Seconds" episode indeed has very little to do with SMA being part of popular culture. Book is not notable. "39 Pounds of Love", on the other hand, should stay IMHO - it is a notable film that centers around this medical condition of the main character. Link to category can stay, nothing wrong with that, you don't need sources for wikilinks. — kashmiri  TALK  08:15, 7 April 2017 (UTC)
 * Independent RS is needed to show it is DUE in a given article.  Per MEDORDER we generally only have these sections if there are sources that show that whatever is discussed had some significant impact on the history of the condition.  Otherwise it becomes an indiscriminate list of random stuff, and gossip.  Jytdog (talk) 01:39, 16 April 2017 (UTC)
 * Not entirely, there is much more to this section - it allows to present the condition's wider social/cultural dimension; disorder's history is normaly discussed in the History section. RS cannot establish DUE: DUE is always editors' own judgement. In my opinion, if there is a NOTABLE film or piece of art that centers around a rare disorder, this fact not only can but definitely should be mentioned in a good encylopaedic article on that disorder. It is not gossip and no, we don't need external sources in order to sum up one Wikipedia article within another. — kashmiri  TALK  12:43, 16 April 2017 (UTC)
 * What ref shows that any one of these had an impact on the history of the condition? Jytdog (talk) 21:35, 16 April 2017 (UTC)
 * "impact on the history of the condition" - where did you get this "requirement" from? — kashmiri  TALK  11:44, 17 April 2017 (UTC)
 * This is what MEDMOS talks about. Jytdog (talk) 17:37, 17 April 2017 (UTC)

Educational assignment
Which sections will I prioritize? Will add a Patient Community section and work on Management section. Also Include an MR image of spinal cord

What resources do I intend to look up, and when? Meta-analysis, PubMed Central & Radiographics. 11/20/17

How will I decide what things (signs, symptoms, side-effects, etc.) to explicitly include? To explicitly exclude? By the Systematic review's data

Will I also embed additional links to other Wiki pages? Most likely, I will as the plan unfolds.

How will I ensure I avoid "doctor-speak" and not use jargon? By using the guidelines from: Writing for the Public, Health Literacy and Translation lecture. As well as University of Michigan plain language medical dictionary and from the CDC. Anderclamusc (talk) 20:02, 20 November 2017 (UTC)


 * Hi, thanks for your initiative to improve this article. Just a quick word that the article is watched by a couple of experienced editors from WikiProject Medicine, so I suggest that you discuss any major changes here on Talk page first.
 * Traditionally there has been strong opposition here against adding "patient community" sections or links to patient groups, as such links may sometimes be construed as endorsement of that organisation or the information it provides. While this might not be much of a threat as regards SMA organisations, the sheer number of organised SMA patient communities (40 countries or more) might complicate your task.
 * Imagery: A spine radiogramme will be of limited use since SMA is primarily a motoneuron disease with the primary pathological changes situated in motoneurons and neuromuscular junctions; secondary changes in muscles, too. However, if you were able to locate a suitable image depicting those neuronal changes as well as patients, that would be very helpful (but keep WP:C in mind).
 * As regards systematic reviews, thank you to focus on publications no older than 2005. They are aplenty, and the progress of medical knowledge in SMA has been tremendous in recent years. In fact, there are many published reviews from 2010+ (please focus on those published by large academic centres in Europe and USA in peer-reviewed journals, esp. Neurological Disorders and Neurology).
 * Hope this will be of help. I am looking forward to your contributions. Regards, — kashmiri  TALK  13:29, 21 November 2017 (UTC)


 * Hey, I appreciate your comments. What suggestions do you/experienced editors have in regards to "patient community" section?(patient community was not exactly what I meant, but obviously what I wrote(I was given very limited time to come up with this educational idea). I have an individual/close personally who is going to help who has given talks at national(USA) SMA meetings and is highly involved in experimental treatment, community efforts to raise money for research and experience with inumerable other aspects of SMA patient management. However, this individual is not a lisenced physician in any country. In your opinion, is there a place/section on this page for daily patient management, clinical research including experimental trials, fundraising, advocacy, etc.?
 * In regards to imaging, my idea was to include an MR of SMA complications( I listed in my objective, MR of the cord. But will search for as much as I can). None would not be specific for SMA as far as I know (I do not know any that would be, as like you said, its a LMN disease. But I think it could improve the page. Your thoughts and suggestions are welcomed. Thanks for the origional reply to my ideas.Anderclamusc (talk) 20:51, 25 November 2017 (UTC)


 * Which sections will I prioritize? Management section(Especially Nutrition & Respiratory with Data from Review Articles from many contributors including Schroth and Wang). Add radiographs(X-ray) of skeletal(thoracic, lumbar, pelvis) abnormalities as a complication and of growth rods in Orthopedics subsection of Management. An MR image of spinal cord showing anterior horn of SMA and of comparable aged individual. Also, add/support the Screening section to expand what and how as well as Prognosis section.


 * What resources do I intend to look up, and when? Meta-analysis, PubMed Central, curesma funded publications, uptodate,dynamed


 * Will I also embed additional links to other Wiki pages? to the free articles, curesma website.Anderclamusc (talk) 04:55, 26 November 2017 (UTC)


 * Which sections will I prioritize? My edit's of Nutrition & Respiratory subsections of Management section will begin today. Already added radiograph(X-ray) of skeletal complication from a neuromuscular disease similar to severe SMA from the creative commons. Was thinking about adding one more, maybe scoliosis as well. Want to add an MR of LMN of anterior horn of spinal cord. However, can't find one that allows that access without requesting the author, which I do not think I have the time to wait for.
 * What resources do I intend to look up, and when? I have all of the articles I believe necessary to improve the 2 subsections of Management in my plan
 * Will I also embed additional links to other Wiki pages? to the curesma.orgAnderclamusc (talk) 01:42, 5 December 2017 (UTC)


 * ===Peer Review===
 * Hi Anderclamusc! I have gone over this article and am submitting to you a peer evaluation as part of a WikiEd course. You have clearly chosen a topic of high complexity with many viewpoints that continue to evolve over time as we learn more about this disease. The content and organization you have contributed has undoubtedly improved the clarity and overall relevance to the topic at hand. Despite there being a multitude of tangents an editor could devote space to, you have excelled at maintaining the momentum of the article.


 * The article could continue to benefit by modifying the language so that it becomes even easier for the lay-reader to understand. For example the introduction contains words that I know my dear mother would not understand. Words such as eukaryotic, atrophy, proximal, autosomal recessive, etc. This continues throughout the rest of the article. Due to the complexity combined with the watchfulness of other WP edititors, it may prove difficult to alter it from it’s present verbage.


 * Some aspects of the article that I found mildly distracting wasin the organization of the article headings. I feel that describing “causes” followed by “signs and symptoms” would help the article flow more logically. In addition, “management and treatment” could potentially be combined under one heading. Overalll the article reads in a balanced and neutral tone. The citations throughout make great use of current reviews and guidelines. There remains a handful of facts that could be better supported by including references or citations.


 * Overall most of the evidence can be traced to the past 5-7 years however there remain a handful of references that could stand to be updated. Again, wonderful job and thank you so much for your effort in improving this article for many to come! Sincerely, Averstumor (talk) 06:05, 11 December 2017 (UTC)


 * Excellent points Averstumor. Good idea, I was looking at the intro and thinking the same thing but did not want to step on too many toes and bite off more than I could chew. I will try my best to edit the intro like you suggested. I will incorporate an explanation in parentheses in some cases and rewrite parts so that an individuals first impression is more clear without explinations to every tenth word. I know individuals who their child received the diagnosis of SMA and came to this article and found it useless. And one individual had a PhD in a field of medicine.


 * In regards to the order of the sections you mentioned. I agree, it seems more logical the way you suggested.


 * I thought about combining the management and treatment sections. From my perspective I think there is overlap in the management and treatment of SMA. So that proactive management of respiratory care or nutrition is the treatment for the progression of the disease to complications where definitive treatment is the standard of care(exceptions of course). Like the analogy, a good defense is a great offence. I thought I would be repeating the same information over and over unless I put in there "see xyzadv subsection" over and over. Since each individual with SMA, even the same type will not have the same disease manifestations or severity(exceptions of course). I thought treatment had its place and I was really to trying hone in on "proactive management" as the best the best way to increase quality of life and life expactancy for most most individuals. And keep treatment as something to turn to when proactive management was not enough or when morbidity was bad. I just do not think the language was neutral enough for me to say. Seems to be such a fine line, because most of the leading authorities in the US use and promote and use proactive management, pharm and the new better technology is the best way to increase quality of life and life expectancy(exceptions of course). I could be wrong about proactive management being opinionated and/or persuasive.


 * I agree that some references could be updated. However, an extensive book on everything SMA was just published in 2017, which referenced most of the original sources in the article. I think you are right, this was a challenging article because of so much individual variability minus the classic hypotonia, etc. in the more severe types. I will try and hit on some of them but really wanted to focus on the prognosis sources. I believe that will have the most impact on a parent who turns to this article with a newly diagnosed child with SMA and sees in black in white that their child will most likely die within "X" years when that has been changing for the better due to the before mentioned.2602:30A:2CD9:7640:140E:1583:666A:3DF7 (talk) 07:05, 12 December 2017 (UTC)Anderclamusc (talk) 07:09, 12 December 2017 (UTC)


 * Averstumor, I have edited some of the into to make it more understandable to the general population. updated some of the references. Rearranged he 2 sections you mentioned. Touched a little bit on newborn screening and added the proponent side since it is still controversial. Anderclamusc (talk) 22:37, 12 December 2017 (UTC)


 * Averstumor, Polished up my final edits to the article and added some information to the prognosis section.Anderclamusc (talk) 05:12, 13 December 2017 (UTC)

Valproic acid
Hi I reverted your addition of VPA under "Treatments" for two reasons: 1. The source you added as a reference nowhere claims that VPA can be used as an "co-adjuvant" (there is no such term in medicine, by the way). This was likely your own conclusion which the source did not state. However, we cannot use original research on Wikipedia. The second problem is that hearsay ("anecdotal evidence") is not an appropriate source of medical information for an encyclopaedia, even if quoted elsewhere – please take time to read Indentifying reliable sources in medicine-related articles. I will try to add the publication to the Valproate section, though – thanks for the link. — kashmīrī  TALK  13:38, 24 March 2019 (UTC)
 * Additionally, on further reading, the article suffers from several methodological limitations. As a matter of fact, the paper's conclusions do not seem to be supported by the preceding analisis. Unfortunately I have no time to discuss the details at the moment, but I flatly reject the conclusions of "VPA improving gross motor function without improving motor function scores", a self-contradictory proposition in which authors obviously tried to reconcile the seemingly positive results of the two very small open-label studies (a combined of 29 patients) from relatively unknown hospitals (in Brazil, Japan and Egypt) with the negative results of four large RCTs (hundreds of patients in total) carried out by renowned experts in major global centers of SMA research (Italy, USA). To give equal weight to each of those trials (esp. when one of the small trials was based on a non-validated Barthel score) and to a German biochemistry trial which did not measure motor function at all, is a serious methodological flaw. A paper just for the sake of having something published, it seems. — kashmīrī  TALK  15:45, 24 March 2019 (UTC)
 * , I understand you are one of the paper's authors, correct? — kashmīrī  TALK  20:07, 24 March 2019 (UTC)

Age that it is a leading cause of death
Ref says "a leading genetic cause of infant mortality" ie in babies. Doc James (talk · contribs · email) 15:13, 7 June 2019 (UTC)
 * "Infant" is not the same as "baby" - an infant is a child up to 1 year of age; whilst the term baby is undefined and can mean anything, really. — kashmīrī  TALK  17:21, 7 June 2019 (UTC) =

congenital heart disease
Not sure why this was removed? Ref says "Some infants with spinal muscular atrophy type 0 also have heart defects that are present from birth (congenital)." https://ghr.nlm.nih.gov/condition/spinal-muscular-atrophy Doc James  (talk · contribs · email) 15:14, 7 June 2019 (UTC)
 * Because it has been reported only in Type 0 SMA which is extremely rare - as of 2016, "only 37 patients corresponding to this very severe form of SMA, characterized by fetal onset and diagnosis at birth, have been reported" . By the way, I was wrong to say in edit summary that there are only two reports, since Saugier-Veber's article (above) mentions that 9 out of 13 cases where ECG was performed had cardiological problems. Still, in an overall picture of the disease, mentioning heart defects in the lead simply because they have been described somewhere for a very rare form would be akin to publication bias. — kashmīrī  TALK  17:04, 7 June 2019 (UTC)

Restored prior lead as

 * Lead is supposed to be 3 to 4 paragraphs not 7
 * Many of the changes were unreferenced such as "It may also appear later in life and then have a milder course of the disease. The age of onset and the severity of symptoms form the basis of the traditional classification of spinal muscular atrophy into four or five types." / "Another gene, SMN2, is considered a disease modifying gene, since usually the more the SMN2 copies, the milder is the disease course." / "While SMA can be diagnosed based on the patient's appearance, the final determination is normally done through genetic testing which usually includes both the SMN1 and SMN2 genes."
 * This block of text was added to the lead

"Medications that address the genetic cause of the disease and stop or reverse its course include nusinersen (Spinraza), which is injected into the spinal cavity, and the gene therapy medication onasemnogene abeparvovec (Zolgensma), which is administered intravenously in small children. More medications are in clinical development. Other treatments include supportive care such as physical therapy, respiratory support (usually in the form of non-invasive ventilation), nutritional support, orthopaedic interventions, and mobility support."

But the reference behind it does not support it.

This "The introduction of pharmacological treatments in 2016 has significantly improved the outcomes and greatly reduced the mortality. Administration of new treatments prior to the onset of first symptoms is thought to prevent the disease altogether." is based on

A review

Which does not say that these have "significantly improved and greatly reduced the mortality"

And this is a primary source

This text was added "Usually, the mutation in the SMN1 gene is inherited from both parents in an autosomal recessive manner, although in around 3% of cases it occurs spontaneously (de novo).

Ref does not say 3% occur de novo.

Also we generally just use generic names with the brandnames going at the article in question. Doc James (talk · contribs · email) 06:41, 4 May 2020 (UTC)


 * One, there is no limit to the number of paragraphs in the lead section, and you cannot revert something just because it doesn't fit your idea of a lede. Two, I mentioned that I will add references later. None of my addition was controversial, so it would do good if you tried to help with adding references instead of summarily reverting what was over an hour of my work. Three, you have invented that SMA is a "group of disorders" in one of your former edits, but I am sorry to say that this is not only unsourced and plainly wrong but also shows that you have little idea about the disorder. Hint: read the hatnote. Four, the article relied too much on an oudated NINDS article, and my aim was to have an improvement based on academic publications.
 * If you truly want to help in this article - to-date, your edits have mostly degraded its quality - I am happy to point you to some high-quality academic sources. If you have a spare two or three hours, you are welcome to summarise the information. For now, your NINDS-based simplification just has to go. — kashmīrī  TALK  19:09, 4 May 2020 (UTC)

With respect to "although in around 3% of cases it occurs spontaneously (de novo)" is unclear. I have found a reference and added "In 2% of cases, one of the mutations occurs during early development and one is inherited from a parent."
 * There are virtually hundred of sources for the 3% of de novo mutations. I will add them in spare time later this week. Until then I see no reason why incorrect informations should be there.
 * We use INN names as article titles. In the text, we can use the common name, esp. if the drug exists only under one brand. See this. — kashmīrī  TALK  19:18, 4 May 2020 (UTC)
 * We have WP:LEAD. Seven paragraphs is not what is recommended.
 * Per WP:V please add references as you go. It is difficult to discuss text and what weight it should be given when no references are provided. Doc James  (talk · contribs · email) 04:35, 5 May 2020 (UTC)

I am happy to collaborate on updating this but based on sources. Doc James (talk · contribs · email) 04:42, 5 May 2020 (UTC)
 * If you think early development is too non specific, happy to go with "during egg and sperm development", though I imagine their are mosaic versions were the error occurs during embryogenesis. Doc James  (talk · contribs · email) 05:23, 5 May 2020 (UTC)