1. Angelman Syndrome “Happy Puppet Syndrome” Melissa C Trimble NS215 – 07/29/2010

2. Definition Angelman Syndrome is a genetic, neurological disorder in chromosome 15. Children with Angelman Syndrome are missing part of their chromosome 15. AS occurs in one in every 10,000- 25,000 children. Harry Angelman, a pediatrician, first discovered AS in 1965. Dr. Angelman had three children come into his clinic in England with similar characteristics which lead him to the discovery that there must be a link. (Anon., 2009b) In 1970 they isolated chromosome 15 and discovered the lack of the gene. (Anon., 2009b)

3. Symptoms Children with AS have developmental delays, intellectual disability, severe speech impairments, problems with movement and balance, recurrent seizures, and a small cranium size. Delayed development becomes readily noticeable at the age of 6 to 12 months. (Anon., 2007) These children are often excitable, happy and they frequently smile, laugh and have hand flapping movements. Hyperactivity and short attention spans are common. Most affected children have trouble sleeping and need less sleep than normal children. (Anon., 2007) As the syndrome progresses the individuals will have continued intellectual disabilities, severe speech impediments and seizures. (Anon., 2007)

4. Progression Pictures Evan Samson has become the face of Angelman Syndrome and his progression has been documented by his parents for AS research. (Samson, 2010)

5. Causes Angelman Syndrome results in the loss of function or even absence of the UBE3A gene. The mother and the father of the affected pass one UBE3A gene. Genomic imprinting; however, will cause one of the genes in the brain to become dormant. An example of the missing gene is below. (Medne, 2000) (Medne, 2000)

6. Pedigree Chart (Anon, n.d.e)

7. Risks/Complications Several risks and complications have been discovered within AS, but this does not diminish life expectancy. (Clayton-Smith, 2009) Complications and Risks: Seizures Gastrointestinal issues Oral motor behaviors Gait and movement disorders Abnormal spinal curvature – scoliosis Often misdiagnosed to be Autism and is often aligned with Autism and Prader-Willi Students and adults with AS need Applied Behavior Analysis (ABA) to help the individual, physical prompting and cues are not necessary as they will become dependent upon them, but reinforcement, modeling, shaping, multiple trials, etc. will be successful. (Anon., n.d.c)

8. Testing/Diagnosis FISH testing or Fluorescent In Situ Hybridization test lights up the critical area on chromosome 15, so it stands out immediately and the absence of the lighted area shows the absence of chromosome 15 and therefore a diagnosis can be determined. (Anon., n.d.d) (Anon., n.d.d)

9. Treatments/Drugs Because there isn't a way to repair chromosome defects, there's no cure for Angelman syndrome. Treatment focuses on managing the medical and developmental problems that the chromosome defects cause. (Anon., 2009c) Anti-seizure medication. Medication may be necessary to control seizures caused by Angelman syndrome. (Anon., 2009c) Physical therapy. Children with Angelman syndrome may learn to walk better and overcome other movement problems with the help of physical therapy. (Anon., 2009c) Communication therapy. Although people with Angelman syndrome usually don't develop verbal language beyond simple sentences, communication therapy can be helpful. Nonverbal language skills may be developed through sign language and picture communication. (Anon., 2009c) Behavior therapy. Behavior therapy can help children with Angelman syndrome overcome hyperactivity and a short attention span, which can aid in developmental progress. Although the level of development people with Angelman syndrome can achieve varies widely, many are outgoing and are able to build relationships with friends and family. (Anon., 2009c)

10. Research Edwin Weeber, PhD, and his colleagues reversed the neurological deficits in a mouse model of AS by inhibiting CaMKII, an enzyme expressed in the area of the brain affected with AS. Dr. Weeber is a researcher in the Vanderbilt Kennedy Center for Research on Human Development. (Marino, 2010) Dr. Weeber and his colleagues found that UBE3A gene is a “housekeeping” gene or a cellular garbage disposal, proteasome. (Marino, 2010) “The most difficult thing to rationalize was that this housekeeping gene — which nobody thought did anything — caused severe mental retardation.” (Marino, 2010) (MARINO, 2010)

11. Research They found that, in Angelman syndrome, CaMKII activity was reduced due to an inhibitory chemical modification (phosphorylation). Because of CaMKII's prominent role in neuronal function, Dr. Weeber suspected that this might account for many of the neurological deficits seen in Angelman syndrome children. (Marino, 2010) In their research they created a mouse with a mutation that prevented the inhibition of CaMKII. They did a cross of two of these mice and found a double mutation of CaMKII and these mice had normal motor and learning functions but had some low seizure activity. (Marino, 2010) “It's very conceivable that if we can figure out what lies between UBE3A and CaMKII — and if it's a specific path — then that could be a therapeutic target.” (Marino, 2010) (MARINO, 2010)

12. Fundraising Many walks throughout the country happen and if you’d like to get involved the closest walk to Kansas City is in St. Louis. The Angelman Syndrome Foundation is very proactive in assisting with the research into AS and has made significant strides. Colin Farrell’s son has Angelman Syndrome and has been an ongoing advocate to find and fund the search for a cure. (Sugar, 2008) (Anon., 2009a)

13. References Cited Anon. 2007. NINDS Angelman Syndrome Information Page. National Institute of Neurological Disorders and Stroke. [Online] National Institute of Health, February 08, 2007. [Cited: July 12, 2010.] http://www.ninds.nih.gov/disorders/angelman/angelman.htm.http://www.ninds.nih.gov/disorders/angelman/angelman.htm Anon. 2009a. Angelman syndrome. Genetics Home Reference. [Online] U.S. National Library of Medicine, July 2009. [Cited: July 12, 2010.] http://ghr.nlm/nih.gov/condition/angelman- syndrome.http://ghr.nlm/nih.gov/condition/angelman- syndrome Anon. 2009b. Harry Angelman and the History of AS. Angelman Syndrome Foundation, Inc. [Online] Angelman Syndrome Foundation, Inc., 2009. [Cited: July 12, 2010.] http://www.angelman.org/stay-informed/facts-about-angelman-syndrome---7th- edition/harry-angelman-and-the-history-of-as. http://www.angelman.org/stay-informed/facts-about-angelman-syndrome---7th- edition/harry-angelman-and-the-history-of-as Anon. 2009c. Angelman syndrome. MayoClinic.com. [Online] Mayo Foundation for Medical Education and Research, December 18, 2009. [Cited: July 18, 2010.] http://www.mayoclinic.com/health/angelman-syndrome/DS01048. http://www.mayoclinic.com/health/angelman-syndrome/DS01048 Anon. n.d.c. Education. Angelman Syndrome Foundation, Inc. [Online] Angelman Syndrome Foundation, Inc., n.d. [Cited: July 12, 2010.] http://www.angelman.org/stay- informed/facts-about-angelman-syndrome---7th-edition/education.http://www.angelman.org/stay- informed/facts-about-angelman-syndrome---7th-edition/education Anon. n.d.d. Genetic Diagnostic Testing. Angelman Syndrome Foundation, Inc. [Online] Angelman Syndrome Foundation, Inc., n.d. [Cited: July 12, 2010.] http://www.angelman.org/stay-informed/facts-about-angelamn-syndrome---7th- edition/genetic-diagnostic-testing. http://www.angelman.org/stay-informed/facts-about-angelamn-syndrome---7th- edition/genetic-diagnostic-testing Anon. n.d.e. Equation 88 png. herkules. [Online] oulu, n.d. [Cited: July 12, 2010.] http://herkules.oulu.fi/isbn9514270274/html/equation88.png. ISBN9514270274. http://herkules.oulu.fi/isbn9514270274/html/equation88.png. ISBN9514270274

14. References Cited Clayton-Smith, J. 2009. Adult Health and Life Expectancy. Angelman Syndrome Foundation, Inc. [Online] Angelman Syndrome Foundation, Inc., 2009. [Cited: July 12, 2010.] http://www.angelman.org/stay-informed/facts-about-angelman-syndrome---7th- edition/adult-health-and-life-expectancy.http://www.angelman.org/stay-informed/facts-about-angelman-syndrome---7th- edition/adult-health-and-life-expectancy Marino, M. 2010. Genetic engineering cures mice of brain disorder. Reporter. [Online] 2010. [Cited: July 29, 2010.] http://www.mc.vanderbilt.edu/reporter/index.html?ID=5323. http://www.mc.vanderbilt.edu/reporter/index.html?ID=5323 Medne, L. 2000. The UBE3A Gene and its Role in Angelman Syndrome. Angelman New Zealand, Inc. [Online] TE&PJ Contractors Ltd., April 2000. [Cited: July 12, 2010.] http://www.angelman.co.nz/about.htm. http://www.angelman.co.nz/about.htm Priddy, L. 2005. Facts about Angelman Syndrome. Super Duper Handy Handouts! [Online] Super Duper Publications, 2005. [Cited: July 29, 2010.] www.superduperinc.com.www.superduperinc.com Samson, E. 2010. Evan Samson. Angelman Syndrome of Nevada. [Online] 2010. [Cited: July 12, 2010.] http://angelmansyndromeofnevada.com/evan.htm.http://angelmansyndromeofnevada.com/evan.htm Sugar, B. 2008. Sugar Daddy Colin Farrell. Mommy's Little Helper - LilSugar. [Online] Bauer-Griffin, February 28, 2008. [Cited: July 12, 2010.] http://www.lilsugar.com/Colin- Farrell-Speaks-Out-About-Angelman-Syndrome-1074907.http://www.lilsugar.com/Colin- Farrell-Speaks-Out-About-Angelman-Syndrome-1074907

15. Questions?