Angelman Syndrome: Difference between revisions
No edit summary |
No edit summary |
||
| Line 9: | Line 9: | ||
== Prevalence == | == Prevalence == | ||
Estimated incidence of 1 in every 12000-20000 live births; with males and females being affected equally <ref>Williams CA, Driscoll DJ, Dagli AI. Clinical and genetic aspects of Angelman syndrome. Genetics in Medicine. 2010 Jul;12(7):385. http://dx.doi.org/10.1097/GIM.0b013e3181def138</ref>. Cases have been reported all over the world, with no preference for specific races or populations (Dagli) | |||
== Epidemiology == | == Epidemiology == | ||
* | * Some delayed developmental can be observed at 6-12 months while other common symptoms usually occur before the age of 3 <ref name=":0">Margolis SS, Sell GL, Zbinden MA, Bird LM. Angelman syndrome. Neurotherapeutics. 2015 Jul 1;12(3):641-50. http://dx.doi.org/10.1007/s13311-015-0361-y</ref> | ||
* Caused by 4 molecular mechanisms <ref>Kishino T, Lalande M, Wagstaff J. UBE3A/E6-AP mutations cause Angelman syndrome. Nature genetics. 1997 Jan;15(1):70. http://dx.doi.org/10.1038/ng0197-70</ref> | * Caused by 4 molecular mechanisms <ref>Kishino T, Lalande M, Wagstaff J. UBE3A/E6-AP mutations cause Angelman syndrome. Nature genetics. 1997 Jan;15(1):70. http://dx.doi.org/10.1038/ng0197-70</ref> | ||
** Maternal deletions of chromosome 15q11-q13 (70-80%) | ** Maternal deletions of chromosome 15q11-q13 (70-80%) | ||
| Line 20: | Line 20: | ||
* Those with deletion have more severe disease and those with UPD and imprinting have less severe defects <ref name=":0" /> | * Those with deletion have more severe disease and those with UPD and imprinting have less severe defects <ref name=":0" /> | ||
* There is typically no family history of the disease as the genetic changes are random events that occur during the formation of the reproductive cells (egg and sperm) or early in development of the embryo <ref name=":1" /> | |||
** However, individuals with AS are capable of reproduction and in one case study with a female, it was observed that she passed the deletion on to her fetus (Lossie) | |||
* Life expectancy of individuals with Angelman Syndrome seems to be close to normal<ref name=":1" /> | |||
== Clinical Presentation == | == Clinical Presentation == | ||
| Line 45: | Line 48: | ||
*** gastroesophageal reflux | *** gastroesophageal reflux | ||
* '''Changes in Presentation with age'''<ref>Genetics Home Reference. Angelman Syndrome. https://ghr.nlm.nih.gov/condition/angelman-syndrome (accessed 2 May 2018)</ref>: | * '''Changes in Presentation with age'''<ref name=":1">Genetics Home Reference. Angelman Syndrome. https://ghr.nlm.nih.gov/condition/angelman-syndrome (accessed 2 May 2018)</ref>: | ||
** As individuals with Angelman Syndrome age they often become less excitable but continue to have intellectual disability, difficulty with speech, and seizures throughout their lives (Genetics Home Reference, 2015). | ** As individuals with Angelman Syndrome age they often become less excitable but continue to have intellectual disability, difficulty with speech, and seizures throughout their lives (Genetics Home Reference, 2015). | ||
Revision as of 20:32, 7 May 2018
Original Editor - Hannah Angermann, Michelle Griffin, Emily Locker
Top Contributors - Hannah Angermann, Kim Jackson, Mande Jooste, Shaimaa Eldib, Rucha Gadgil, Meaghan Rieke, Kirenga Bamurange Liliane and Aminat Abolade
Description of Angelman Syndrome *note: this is a student project that is still being completed[edit | edit source]
Complex genetic disorder affecting the nervous system. It is characterized by severe learning difficulties, motor dysfunction, seizure disorder, and often a happy, sociable disposition.
Prevalence[edit | edit source]
Estimated incidence of 1 in every 12000-20000 live births; with males and females being affected equally [1]. Cases have been reported all over the world, with no preference for specific races or populations (Dagli)
Epidemiology[edit | edit source]
- Some delayed developmental can be observed at 6-12 months while other common symptoms usually occur before the age of 3 [2]
- Caused by 4 molecular mechanisms [3]
- Maternal deletions of chromosome 15q11-q13 (70-80%)
- Intragenic mutation in maternally inherited UBE3A which is found in chromosome 15q11-q13 (10-20%)
- Paternal uniparental disomy (UPD) in chromosome 15q11-q13 (3-5%)
- Imprinting defects in chromosome 15q11-q13 which change the expression of UBE3A (3-5%)
- Those with deletion have more severe disease and those with UPD and imprinting have less severe defects [2]
- There is typically no family history of the disease as the genetic changes are random events that occur during the formation of the reproductive cells (egg and sperm) or early in development of the embryo [4]
- However, individuals with AS are capable of reproduction and in one case study with a female, it was observed that she passed the deletion on to her fetus (Lossie)
- Life expectancy of individuals with Angelman Syndrome seems to be close to normal[4]
Clinical Presentation[edit | edit source]
Video created by Foundation of Angelman Syndrome (FAST), Australia
- Observable Presentation
- Motor Presentation[2]
- tremors, jerkiness, and ataxia
- Loss of balance and wide-based gait
- Behavioural Presentation[2]
- Developmental delay is normally seen within the first year of life
- most patients lack speech completely but those mildly affected can speak a few words
- Severe intellectual disability
- Hyperactivity and short attention span
- Mouthing of objects
- Happy demeanor with increased laughter, and often an attraction to water
- Developmental delay is normally seen within the first year of life
- Additional Comorbidities that present[2]:
- Seizures (60% of individuals)
- Autism spectrum disorder (ASD),
- Digestive system complications
- constipation
- gastroesophageal reflux
- Changes in Presentation with age[4]:
- As individuals with Angelman Syndrome age they often become less excitable but continue to have intellectual disability, difficulty with speech, and seizures throughout their lives (Genetics Home Reference, 2015).
Diagnostic Procedures[edit | edit source]
Angelman Syndrome may first be suspected in infants due to gross delay of motor milestones and/or speech delay[6]. A physiotherapist may consider a diagnosis of Angelman Syndrome based upon a detailed patient history, a thorough clinical evaluation and identification of characteristic findings. In order to confirm a suspected diagnosis genetic testing must be completed via a blood tests such as DNA methylation [2].
Differential Diagnosis[edit | edit source]
| Differential Diagosis | Key Shared Features with AS | Key Distinguishing Features |
|---|---|---|
| Prader-Willi Syndome | Developmental delays | -Extreme feeding problems
-More severe behavioural symptoms such as obsessive-compulsive symptoms |
| Rett Syndrome | Developmental delays, intellectual disability, speech impairment, seizures | -Seen only in females.
-Stereotypical hand movements -Apraxia is more severe with loss of mobility in later stages |
| Mowat-Wilson Syndrom | Delayed motor development, intellectual disability, epilepsy | -Distinct facial features
-Intestinal complications |
| Pitt-Hopkins Syndrome | Happy disposition, speech impairments | -Distinctive hand and facial features
-Self-aggression and violent outbursts |
Outcome Measures
[edit | edit source]
add text here relating to the differential diagnosis of this condition
Physiotherapy Management and Treatment
[edit | edit source]
text here
Additional Treatment[edit | edit source]
- Occupational therapy:
- Play a key role in treating fine motor skills, and self management skills to perform activities of daily living.
- Speech Language Pathology
- Play a key role in treating difficulties with both communication and swallowing.
Clinical Guidelines for Angelman Syndrome[edit | edit source]
For more detailed information on the treatment of Angelman Syndrome across several health care providers, clinical guidelines have been created by the Angelman Syndrome Guideline Development Group. Visit their document here [1].
Additional Resources[edit | edit source]
Canadian Angelman Syndrome Society:
- Visit their webpage here: https://www.angelmancanada.org/
FAST: Foundation of Angelman Syndrome Therapeutics
- Visit their webpage here: https://cureangelman.org/
References[edit | edit source]
- ↑ Williams CA, Driscoll DJ, Dagli AI. Clinical and genetic aspects of Angelman syndrome. Genetics in Medicine. 2010 Jul;12(7):385. http://dx.doi.org/10.1097/GIM.0b013e3181def138
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Margolis SS, Sell GL, Zbinden MA, Bird LM. Angelman syndrome. Neurotherapeutics. 2015 Jul 1;12(3):641-50. http://dx.doi.org/10.1007/s13311-015-0361-y
- ↑ Kishino T, Lalande M, Wagstaff J. UBE3A/E6-AP mutations cause Angelman syndrome. Nature genetics. 1997 Jan;15(1):70. http://dx.doi.org/10.1038/ng0197-70
- ↑ 4.0 4.1 4.2 Genetics Home Reference. Angelman Syndrome. https://ghr.nlm.nih.gov/condition/angelman-syndrome (accessed 2 May 2018)
- ↑ Angelman Syndrome Guideline Development Group. Management of Angelman Syndrome: A Clinical Guideline Version:1. University of Manchester, 2010. https://www.orpha.net/data/patho/Pro/en/AngelmanGuidelines2011.pdf (Accessed 2 May 2018)
- ↑ Williams CA, Beaudet AL, Clayton‐Smith J, Knoll JH, Kyllerman M, Laan LA, Magenis RE, Moncla A, Schinzel AA, Summers JA, Wagstaff J. Angelman syndrome 2005: updated consensus for diagnostic criteria. American journal of medical genetics Part A. 2006 Mar 1;140(5):413-8. https://doi.org/10.1002/ajmg.a.31074
- ↑ Foundation for Angelman Syndrome Therapeutics. Common Misdiagnoses. https://cureangelman.org/understanding-angelman/differential-diagnosis. (Accessed 6 May 2018)
