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Prader-Willi Syndrome - A Rare Genetic Bullet!


There are many acidic symptomologies expressed with the acidic condition of Prader-Willi Syndrome, a rare 'genetic bullet' disorder.
The Prader–Willi Syndrome or PWS is a rare 'genetic bullet' that involves seven genes (or some subset thereof) on chromosome 15 (q 11–13) which are unexpressed (chromosome 15q partial deletion) on the paternal chromosome.
When considering the 'genetic bullet' theory, I relate it to a stupid game called Russian Roulette. In this metaphor a single bullet is placed in the chamber, representing the non-expressed genetics where the trigger that fires the 'genetic bullet' are the acidic lifestyle and dietary choices of the person playing this stupid game. If a person continues to pull the acidic lifestyle and dietary trigger the rare 'genetic bullet' will be fired and symptoms will be expressed. Bottomline 95 percent of ALL sickness and disease is the result of what you think, what you drink and what you eat. The remaining 5 percent is the result of genetics which is affected by what you think, what you drink and what you eat.
Whether or not these seven genes are expressed is directly related to the delicate alkaline pH of the body fluids surrounding these genes. Therefore the expression of ANY gene, is based upon the lifestyle and dietary choices and its affect on the delicate pH of the body fluids.
Internal Environmental Characteristics of PWS
Environmental characteristics of lifestyle and dietary affects that lead to PWS includes the following environmental acidic symptoms of "low muscle tone, short stature, incomplete sexual development, cognitive disabilities, problem behaviors, and a chronic feeling of hunger that can lead to excessive eating and life-threatening obesity."[1]



Uterus and birth symptomologies:

  • Frequent abnormal fetal position
  • Reduced fetal movement
  • Occasional polyhydramnios (excessive amniotic fluid)
  • Often breech or caesarean births
  • Lethargy
  • Hypotonia
  • Feeding difficulties (due to poor muscle tone affecting sucking reflex)
  • Difficulties establishing respiration
  • Hypogonadism


Childhood symptomologies:


  • Excessive sleeping
  • Delayed milestones/intellectual delay
  • Strabismus ('crossed eyes')
  • Scoliosis (often not detected at birth)
  • Cryptorchidism
  • Speech delay
  • Poor physical coordination
  • Hyperphagia (over-eating) begins between the age of 2 and 8, and continues on throughout adulthood. Note change from feeding difficulties in infancy
  • Excessive weight gain
  • Sleep disorders
  • Delayed puberty
  • Short stature
  • Obesity
  • Extreme flexibility

Adulthood symptomologies:


  • Hypogonadism
  • Infertility (males and females)
  • Sparse pubic hair
  • Obesity
  • Hypotonia (low muscle tone)
  • Learning disabilities/borderline intellectual functioning (but some cases of average intelligence)
  • Prone to diabetes mellitus (Type I Diabetes)
  • Extreme flexibility

Physical appearance symptomologies:


  • Small hands and feet with tapering of fingers
  • Prominent nasal bridge
  • Soft skin, which is easily bruised
  • Excess fat, especially in the central portion of the body
  • High, narrow forehead
  • Thin upper lip
  • Downturned mouth
  • Almond-shaped eyes
  • Light skin and hair relative to other family members
  • Lack of complete sexual development
  • Frequent skin picking
  • Striae
  • Delayed motor development

Neuro-cognitive symptomologies:

Individuals with PWS are at risk of learning and attention difficulties. Curfs and Fryns (1992) conducted research into the varying degrees of learning disability found in PWS.  Their results, using a measure of IQ, were as follows:
  • 5%: IQ above 85 (high to low average intelligence)
  • 27%: IQ 70 – 85 (borderline intellectual functioning)
  • 39%: IQ 50 – 70 (mild intellectual disability)
  • 27%: IQ 35 – 50 (moderate intellectual disability)
  • 1%: IQ 20 – 35 (severe intellectual disability)
Cassidy found that 40% of individuals with PWS have borderline/low average intelligence, a figure higher than the 32% found in Curfs and Fryns' study.   However, both studies suggest that most individuals (50–65%) fall within the mild/borderline/low average intelligence range.
Parents report that some children have IQ's greater than 110 function normally in school.
Children with PWS show an unusual cognitive profile. They are often strong in visual organization and perception, including reading and vocabulary, but their spoken language (sometimes affected by hypernasality) is generally poorer than their comprehension. A marked skill in completing jigsaw puzzles has been noted,[4][5] but this may be an effect of increased practice.[6]
Auditory information processing and sequential processing are relatively poor, as are arithmetic and writing skills, visual and auditory short-term memory and auditory attention span. These sometimes improve with age, but deficits in these areas remain throughout adulthood.[7]

Prader–Willi syndrome is also frequently associated with an extreme and insatiable appetite, often resulting in morbid acidic obesity build-up in the fatty tissues. It is the most common genetic trigger that causes morbid obesity in children of which is also associated with congestion or consptipation of the small and large bowel due to the ingestion of animal flesh, dairy products and lots of bread.[8]  

Currently there is no consensus as to the cause for this particular symptom, although acidic lifestyles and diets can trigger genetic abnormalities in chromosome 15 and disrupt the normal functioning of the hypothalamus.[9] Given that the hypothalamus arcuate nucleus regulates many basic processes, including appetite, there may well be a link. In the hypothalamus of people with PWS, nerve cells that produce oxytocin, an acidic waste product or hormone from the function of the hypothalamus, is thought to contribute to satiety and has been found to be abnormal in PWS people.

Behavioral

People with Prader–Willi syndrome have high ghrelin levels, an acidic hormone which is thought to directly contribute to the increased appetite, hyperphagia, and obesity seen in this gene activated syndrome. Cassidy states the need for a clear delineation of behavioral expectations, the reinforcement of behavioural limits and the establishment of regular routines.
The main mental health difficulties experienced by people with PWS include compulsive behaviour (usually manifested in skin-picking) and anxiety.[8][12] Psychiatric symptoms, for example, hallucinations, paranoia and depression, have been described in some cases[8] and affect approximately 5–10% of young adults.[7] Psychiatric and behavioural problems are the most common cause of hospitalization.[8]

There are several aspects of PWS that support the concept of reduced glandular function that affects growth, demonstated by reduced hormones in individuals with PWS. Specifically, individuals with PWS have short stature, are obese with abnormal body composition, have reduced fat free mass (FFM), have reduced lean body mass (LBM) and total energy expenditure, and have decreased bone density.

Endocrine


PWS is characterized by hypogonadism. This is manifested as undescended testes in males and benign premature adrenarche in females. Testes may descend with time or can be managed with surgery or testosterone replacement. Adrenarche may be treated with hormone replacement therapy.

Ophthalmologic


PWS is commonly associated with development of strabismus. In one study,[9] over 50% of patients had strabismus, mainly esotropia.

Genetics



PWS is caused by the non-expression of the paternal copies of the SNRPN andnecdin genes along with clusters of snoRNAs: SNORD64, SNORD107, SNORD108 and two copies of SNORD109, 29 copies of SNORD116 (HBII-85) and 48 copies of SNORD115 (HBII-52). These are on chromosome 15 located in the region 15q11-13.[10][11][12] 

This so-called PWS/AS region may be lost by one of several genetic mechanisms which, in the majority of instances occurs through change in pH or increased acidity which leads to mutation. Other less common mechanisms include; uniparental disomy, sporadic acidic mutations, chromosome translocations, and gene non-expression. Due to imprinting, the maternally inherited copies of these genes are virtually silent, only the paternal copies of the genes are expressed. [13] PWS results from the loss of paternal copies of this region. Non-expression of the same region on the maternal chromosome causes Angelman syndrome (AS). PWS and AS represent the first reported instances of imprinting disorders in humans.

The risk to the sibling of an affected child of having PWS depends upon the lifestyle and dietary trigger that caused the non-expression of the genetic mechanism. The risk to siblings is There are many acidic symptomologies expressed with the acidic condition of Prader-Willi Syndrome, a rare 'genetic bullet' disorder. The Prader–Willi syndrome or PWS is a rare genetic bullet that involves seven genes (or some subset thereof) on chromosome 15 (q 11–13) which are unexpressed (chromosome 15q partial deletion) on the paternal chromosome.  

Prenatal testing is possible for any of the known genetic mechanisms.
Angelman.PNG

A microdeletion in one family of the snoRNA HBII-52 has excluded it from playing a major role in the disease.[14]
Studies of human and mouse model systems have shown that non-expression of the 29 copies of the C/D box snoRNA SNORD116 (HBII-85) has been shown to be the primary cause of Prader–Willi syndrome.[15][16][17][18][19]

Diagnosis


Traditionally, Prader–Willi syndrome was diagnosed by clinical presentation. Currently, the syndrome is diagnosed through genetic testing; testing is recommended for newborns with pronounced hypotonia. Early diagnosis of PWS allows for early intervention as well as the early increased amounts of alkaline green foods, green drinks, alkaline mineral salts, alkaline water, and polyunsaturated plant oils will increase healthy endocrine function and increased amounts of growth hormone. Daily recombinant growth hormone (GH) injections may also be indicated for children with PWS. A healthy active endocrine system, especially a health Hypothalmus will show increased GH, supporting linear growth and increased muscle mass, and may lessen food preoccupation and weight gain.
PWS affects approximately 1 in 10,000 to 1 in 25,000 newborns.[20] There are more than 400,000 people who live with PWS around the world.[21] It is traditionally characterized by hypotonia, short stature,hyperphagia, obesity, behavioral issues (specifically OCD-like behaviors), small hands and feet,hypogonadism, and mild intellectual disability.[20]However, with early diagnosis and early treatment (such as with growth hormone therapy), the prognosis for persons with PWS is beginning to change. Like autism, PWS is a spectrum disorder and so symptoms can range from mild to severe, and may change throughout the person's lifetime. Various organ systems are affected.
The mainstay of diagnosis is genetic testing, specifically DNA-based methylation testing to detect the absence of the paternally contributed Prader–Willi syndrome/Angelman syndrome(PWS/AS) region on chromosome 15q11-q13. Such testing detects over 97% of cases. Methylation-specific testing is important to confirm the diagnosis of PWS in all individuals, but especially those who are too young to manifest sufficient features to make the diagnosis on clinical grounds or in those individuals who have atypical findings.
Prader–Willi syndrome is often misdiagnosed as a variety of other syndromes due to many in the medical community's unfamiliarity with PWS. Sometimes it is misdiagnosed as Down syndrome, simply because of the relative frequency of Down syndrome compared to PWS.

Treatment

Prader–Willi syndrome according to current medical savants has no cure; however, several alkalizing treatments and alkalizing diet plans are in place to lessen the condition's and reverse many of the acidic symptoms. During infancy, subjects should undergo alkalizing therapies, such as lymphatic massage and colon hydrotherapy to improve muscle tone, bowel elimination, improved cognitive function, prevention of diabetes, improved learning, and reduced over-eating. 

Speech and occupational therapy are also indicated. During the school years, children benefit from a highly structured learning environment as well as extra help. The largest problem associated with the syndrome is severe obesity.
Natural alkaline foods and supplements, including mineral salts, cholorphyll, polyunsaturated oils, and alkaline water support the endocrine system that allows for normal hypothalmus function and the release of daily growth hormone for children with PWS. An alkaline lifestyle and diet supports linear growth and increased muscle mass, and may lessen food preoccupation and weight gain.[21][22][23]
Because of severe obesity, obstructive sleep apnea is a common sequela, and a positive airway pressure machine may be needed. Patients with Prader–Willi syndrome have a very high tolerance to pain; therefore they may be experiencing significant abdominal symptoms such as acute gastritis, appendicitis, or cholecystitis and not be aware of it until later.  Here I recommend full-body Ultrasound and thermography with live and blood cell anaylsis to determine anatomical, physiological and functional problems so they can be corrected with an alkaline lifestyle and diet.

Society and Culture

Despite its rarity, Prader–Willi syndrome has been often referenced in popular culture, partly due to the fascination surrounding the insatiable appetite and obesity that are symptoms of the syndrome.
Prader–Willi syndrome has been depicted and documented several times in television. A fictional individual with Prader-Willi Syndrome featured in the episode entitled "Dog Eat Dog" of the television series CSI: Crime Scene Investigation, which aired on November 24, 2005.[24] In the UK media in July 2007, Channel 4 aired a 2006 documentary called Can't Stop Eating, surrounding the everyday lives of two people with Prader–Willi syndrome, Joe and Tamara.[25] In the May 9, 2010 episode of Extreme Makeover: Home Edition, Sheryl Crow helped Ty Pennington rebuild a home for a family in which the family's youngest son, Ethan Starkweather, was suffering from Prader-Willi syndrome. [26] In the March 22, 2012 episode of Mystery Diagnosis on the Discovery Health channel, Conor Heybach, who has Prader-Willi syndrome, shared his true story of how he was diagnosed with it. [27]
In December 2011 the Taipei Times, in Taiwan, highlighted the tragedy of a taxi driver who had killed himself and his nine-year-old daughter who had the condition, in what police described as a "probable murder-suicide."[28]
Actress Mayim Bialik — former star of TV's Blossom and currently playing a neuroscientist named Amy Farrah Fowler on The Big Bang Theory — completed her PhD in 2007 with a dissertation on Prader–Willi syndrome, titled,"Hypothalamic regulation in relation to maladaptive, obsessive-compulsive, affiliative, and satiety behaviors in Prader-Willi syndrome." [29] [30][31]
References

  1. Jump up^ "Questions and Answers on Prader-Willi Syndrome". Prader-Willi Syndrome Association. Retrieved February 2, 2012.
  2. ^ Jump up to:a b Curfs LM, Fryns JP (1992). "Prader-Willi syndrome: a review with special attention to the cognitive and behavioral profile". Birth Defects Orig. Artic. Ser. 28 (1): 99–104. PMID 1340242.
  3. ^ Jump up to:a b c Cassidy SB (1997). "Prader-Willi syndrome". Journal of Medical Genetics 34 (11): 917–23. doi:10.1136/jmg.34.11.917. PMC 1051120. PMID 9391886.
  4. nal. Retrieved December 4, 2012.
  5. Jump up^ Clark DJ, Boer H, Webb T (1995). "General and behavioural aspects of PWS: a review".Mental Health Research 8 (195): 38–49.
  6. Jump up^ Cassidy SB, Devi A, Mukaida C (1994). "Aging in PWS: 232 patients over age 30 years".Proc. Greenwood Genetic Centre 13: 102–3.
  7. Jump up^ Hered RW, Rogers S, Zang YF, Biglan AW (1988). "Ophthalmologic features of Prader-Willi syndrome". J Pediatr Ophthalmol Strabismus 25 (3): 145–50. PMID 3397859.
  8. Jump up^ Online 'Mendelian Inheritance in Man' (OMIM) Prader-Willi Syndrome; PWS -17627
  9. Jump up^ de los Santos T, Schweizer J, Rees CA, Francke U (November 2000). "Small evolutionarily conserved RNA, resembling C/D box small nucleolar RNA, is transcribed from PWCR1, a novel imprinted gene in the Prader-Willi deletion region, which Is highly expressed in brain".American Journal of Human Genetics 67 (5): 1067–82. doi:10.1086/303106. PMC 1288549.PMID 11007541.
  10. Jump up^ Cavaillé J, Buiting K, Kiefmann M, Lalande M, Brannan CI, Horsthemke B, Bachellerie JP, Brosius J, Hüttenhofer A (December 2000). "Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization". Proc. Natl. Acad. Sci. U.S.A.. 97 (26): 14311–6. doi:10.1073/pnas.250426397. PMC 18915. PMID 11106375.
  11. Jump up^ http://medicalxpress.com/news/2014-05-major-breakthrough-prader-willi-syndrome-parental.html
  12. Jump up^ Runte M, Varon R, Horn D, Horsthemke B, Buiting K (2005). "Exclusion of the C/D box snoRNA gene cluster HBII-52 from a major role in Prader-Willi syndrome.". Hum Genet 116 (3): 228–30. doi:10.1007/s00439-004-1219-2. PMID 15565282.
  13. Jump up^ Skryabin BV, Gubar LV, Seeger B, Pfeiffer J, Handel S, Robeck T, Karpova E, Rozhdestvensky TS, Brosius J (2007). "Deletion of the MBII-85 snoRNA gene cluster in mice results in postnatal growth retardation". PLoS Genet. 3 (12): e235.doi:10.1371/journal.pgen.0030235. PMC 2323313. PMID 18166085.
  14. Jump up^ Sahoo T, del Gaudio D, German JR, Shinawi M, Peters SU, Person RE, Garnica A, Cheung SW, Beaudet AL (2008). "Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster.". Nat Genet 40 (6): 719–21. doi:10.1038/ng.158.PMC 2705197. PMID 18500341.
  15. Jump up^ Ding F, Li HH, Zhang S, Solomon NM, Camper SA, Cohen P, Francke U (2008). "SnoRNA Snord116 (Pwcr1/MBII-85) deletion causes growth deficiency and hyperphagia in mice". In Akbarian, Schahram. PLoS ONE 3 (3): e1709. doi:10.1371/journal.pone.0001709.PMC 2248623. PMID 18320030.
  16. Jump up^ Ding F, Prints Y, Dhar MS, Johnson DK, Garnacho-Montero C, Nicholls RD, Francke U (2005). "Lack of Pwcr1/MBII-85 snoRNA is critical for neonatal lethality in Prader-Willi syndrome mouse models". Mamm Genome 16 (6): 424–31. doi:10.1007/s00335-005-2460-2.PMID 16075369.
  17. Jump up^ de Smith AJ, Purmann C, Walters RG, Ellis RJ, Holder SE, Van Haelst MM, Brady AF, Fairbrother UL, Dattani M, Keogh JM, Henning E, Yeo GS, O'Rahilly S, Froguel P, Farooqi IS, Blakemore AI (June 2009). "A Deletion of the HBII-85 Class of Small Nucleolar RNAs (snoRNAs) is Associated with Hyperphagia, Obesity and Hypogonadism". Hum. Mol. Genet.18 (17): 3257–65. doi:10.1093/hmg/ddp263. PMC 2722987. PMID 19498035.
  18. ^ Jump up to:a b Killeen, Anthony A. (2004). "Genetic Inheritance". Principles of Molecular Pathology. Humana Press. p. 41. ISBN 978-1-58829-085-4.
  19. Jump up^ Tweed, Katherine (September 2009). "Shawn Cooper Struggles with Prader Willi Syndrome". AOL Health. Retrieved September 2009.
  20. Jump up^ Davies PS, Evans S, Broomhead S, Clough H, Day JM, Laidlaw A, Barnes ND (May 1998)."Effect of growth hormone on height, weight, and body composition in Prader-Willi syndrome". Arch. Dis. Child. 78 (5): 474–6. doi:10.1136/adc.78.5.474. PMC 1717576.PMID 9659098.
  21. Jump up^ Carrel AL, Myers SE, Whitman BY, Allen DB (April 2002). "Benefits of long-term GH therapy in Prader-Willi syndrome: a 4-year study". J. Clin. Endocrinol. Metab. 87 (4): 1581–5.doi:10.1210/jc.87.4.1581. PMID 11932286.
  22. Jump up^ Höybye C, Hilding A, Jacobsson H, Thorén M (May 2003). "Growth hormone treatment improves body composition in adults with Prader-Willi syndrome". Clin. Endocrinol. (Oxf) 58(5): 653–61. doi:10.1046/j.1365-2265.2003.01769.x. PMID 12699450.
  23. Jump up^ Mary Jones. "Case Study: Cataplexy and SOREMPs Without Excessive Daytime Sleepiness in Prader Willi Syndrome. Is This the Beginning of Narcolepsy in a Five Year Old?". European Society of Sleep Technologists. Retrieved April 6, 2009.
  24. Jump up^ "Dog Eat Dog". www.csifiles.com. Retrieved June 12, 2009.
  25. Jump up^ "Can't Stop Eating". 2006. Retrieved June 12, 2009.
  26. Jump up^ http://www.aoltv.com/tag/Extreme+Makeover:+Home+Edition/
  27. Jump up^ http://www.pwsausa.org/Anouncements/March2010-TV.htm
  28. Jump up^ Group urges more support for Prader-Willi sufferers - Taipei Times. Published December 24, 2011. Retrieved May 27, 2012.
  29. Jump up^ http://www.worldcat.org/title/hypothalamic-regulation-in-relation-to-maladaptive-obsessive-compulsive-affiliative-and-satiety-behaviors-in-prader-willi-syndrome/oclc/261564900
  30. Jump up^ "Life After Child Stardom - Not by the Numbers". Abcnews.go.com. November 24, 2006. Retrieved May 27, 2012.
  31. Jump up^ Bialik, Mayim C. "Hypothalamic regulation in relation to maladaptive, obsessive-compulsive, affiliative, and satiety behaviors in Prader-Willi syndrome" (PhD Diss., UCLA, 2007).
 

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