Prader-Willi Syndrome: Difference between revisions

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It is characterized by small hands and feet, abnormal growth and body composition (small stature, early-onset childhood obesity), hypotonia (weak muscles) at birth, hypogonadism, insatiable hunger, extreme obesity, and intellectual disability.
It is characterized by small hands and feet, abnormal growth and body composition (small stature, early-onset childhood obesity), hypotonia (weak muscles) at birth, hypogonadism, insatiable hunger, extreme obesity, and intellectual disability.


== Prevalence and Etiology ==
== Prevalence ==
 
===== Prevalence: =====
PWS affects an estimated 1 in 15,000 - 30,000 people<ref name=":0">Cassidy SB, Driscoll DJ. Prader-Willi syndrome. Eur J Hum Genet. 2009;17(1):3-13. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2985966/ doi: 10.1038/ejhg.2008.165]</ref>. The prevalence rates differ among studies across countries, mainly due to using different methods for case identification. There is no strong evidence for increased risk in specific countries or gene pools. Both sexes appear to be affected equally<ref name=":0" />.
PWS affects an estimated 1 in 15,000 - 30,000 people<ref name=":0">Cassidy SB, Driscoll DJ. Prader-Willi syndrome. Eur J Hum Genet. 2009;17(1):3-13. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2985966/ doi: 10.1038/ejhg.2008.165]</ref>. The prevalence rates differ among studies across countries, mainly due to using different methods for case identification. There is no strong evidence for increased risk in specific countries or gene pools. Both sexes appear to be affected equally<ref name=":0" />.


===== Etiology: =====
== Etiology and Pathological Process ==
People normally inherit one copy of each chromosome from each parent. Some of these genes are turned on (active) only on the copy that is inherited from a person's father (the paternal copy) which is called as genomic imprinting.
People normally inherit one copy of chromosome from each parent except those with sex characteristics. Some of these genes are turned on (active) only on the copy that is inherited from a person's father (the paternal copy) which is called as genomic imprinting.


PWS is caused due to abnormality in the expression of genes on Chromosome 15 specifically on the long arm of chromosome 15q11-q13. This abnormality can be caused due to<ref>Genetics Home Reference. Prader-Willi Syndrome.https://ghr.nlm.nih.gov/condition/prader-willi-syndrome</ref>:
PWS is caused due to abnormality in the expression of genes on Chromosome 15 specifically on the long arm of chromosome 15q11-q13. This abnormality can be caused due to<ref>Genetics Home Reference. Prader-Willi Syndrome.https://ghr.nlm.nih.gov/condition/prader-willi-syndrome</ref>:
# deletion of the genes on the paternal copy  
# deletion of the genes on the paternal copy (70-80%)
# the genes on the maternal copy are turned off (inactive)
# the genes on the maternal copy are turned off (inactive) (20-25%)
# has two copies of chromosome 15 inherited from the mother instead of one copy from each parent (maternal uniparental disomy)
# has two copies of chromosome 15 inherited from the mother instead of one copy from each parent (maternal uniparental disomy) (1%)
# chromosomal rearrangement called a translocation,
# chromosomal rearrangement called a translocation (<1%)
# by a mutation or other defect (Imprinting center defects).
# by a mutation or other defect (Imprinting center defects) (1%)
Prader-Willi syndrome is the first human disorder attributed to genomic imprinting.
 
The PW genes identified are<ref>de los Santos T, Schweizer J, Rees CA, Francke U. 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. Am J Hum Genet. 2000;67(5):1067-1082. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1288549/ doi:10.1086/303106]</ref>:
# ''SNRPN'' and ''NDN'' necdin genes, 
# clusters of snoRNAs: SNORD64, SNORD107, SNORD108 and two copies of SNORD109
There are significant advances in understanding and characterizing the genetic changes associated with PWS that have taken place, though, the exact mechanism by which lack of functional genetic material causes PWS is not understood. Researchers are still studying  the normal role of the genetic sequences in the PWS region and how their loss affects multiple other systems in the body.
 
The genetic changes associated with this disorder present as random events during the formation of reproductive cells or in early embryonic development, with no history of the disorder in the family. Hereditary transmission is also very rarely seen.


== Pathological Process ==
== Clinical Features ==
== Clinical Features ==
== Diagnosis ==
== Diagnosis ==

Revision as of 12:10, 18 September 2020

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What Is Prader-Willi Syndrome?[edit | edit source]

Prader-Willi syndrome (PWS) is a rare genetic disorder that is caused due to abnormal functioning of specific genes on chromosome 15.The condition is named after Swiss physicians Andrea Prader and Heinrich Willi and Alexis Labhart who described it in detail in 1950s. It is also called as Prader-Labhart-Willi, or Prader-Willi-Fanconi syndrome.

It is characterized by small hands and feet, abnormal growth and body composition (small stature, early-onset childhood obesity), hypotonia (weak muscles) at birth, hypogonadism, insatiable hunger, extreme obesity, and intellectual disability.

Prevalence[edit | edit source]

PWS affects an estimated 1 in 15,000 - 30,000 people[1]. The prevalence rates differ among studies across countries, mainly due to using different methods for case identification. There is no strong evidence for increased risk in specific countries or gene pools. Both sexes appear to be affected equally[1].

Etiology and Pathological Process[edit | edit source]

People normally inherit one copy of chromosome from each parent except those with sex characteristics. Some of these genes are turned on (active) only on the copy that is inherited from a person's father (the paternal copy) which is called as genomic imprinting.

PWS is caused due to abnormality in the expression of genes on Chromosome 15 specifically on the long arm of chromosome 15q11-q13. This abnormality can be caused due to[2]:

  1. deletion of the genes on the paternal copy (70-80%)
  2. the genes on the maternal copy are turned off (inactive) (20-25%)
  3. has two copies of chromosome 15 inherited from the mother instead of one copy from each parent (maternal uniparental disomy) (1%)
  4. chromosomal rearrangement called a translocation (<1%)
  5. by a mutation or other defect (Imprinting center defects) (1%)

Prader-Willi syndrome is the first human disorder attributed to genomic imprinting.

The PW genes identified are[3]:

  1. SNRPN and NDN necdin genes,
  2. clusters of snoRNAs: SNORD64, SNORD107, SNORD108 and two copies of SNORD109

There are significant advances in understanding and characterizing the genetic changes associated with PWS that have taken place, though, the exact mechanism by which lack of functional genetic material causes PWS is not understood. Researchers are still studying the normal role of the genetic sequences in the PWS region and how their loss affects multiple other systems in the body.

The genetic changes associated with this disorder present as random events during the formation of reproductive cells or in early embryonic development, with no history of the disorder in the family. Hereditary transmission is also very rarely seen.

Clinical Features[edit | edit source]

Diagnosis[edit | edit source]

Differential Diagnosis[edit | edit source]

Treatment[edit | edit source]

Physiotherapy Treatment[edit | edit source]

Resources[edit | edit source]

  • bulleted list
  • x

or

  1. numbered list
  2. x

References[edit | edit source]

  1. ↑ 1.0 1.1 Cassidy SB, Driscoll DJ. Prader-Willi syndrome. Eur J Hum Genet. 2009;17(1):3-13. doi: 10.1038/ejhg.2008.165
  2. ↑ Genetics Home Reference. Prader-Willi Syndrome.https://ghr.nlm.nih.gov/condition/prader-willi-syndrome
  3. ↑ de los Santos T, Schweizer J, Rees CA, Francke U. 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. Am J Hum Genet. 2000;67(5):1067-1082. doi:10.1086/303106
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