Angelman Syndrome/Prader-Willi Syndrome Nancy Ashour

Definition Angelman Syndrome, also known as Prader-Willi Syndrome, is a genetic disorder which causes neurological and developmental problems. It generally affects the nervous system.

Symptoms slow/delayed development minimal/no speech difficulty  moving/walking/balancing recurrent laughter and smiling excitable, cheerful personality seizures (defined by Healthline as “changes in the brain’s electrical activity”, sometimes causing anxiousness, sickness, dizziness etc.) stiffness/jerkiness (in their movement) small head, which is flat at the back thrusting of tongue light pigmentation (in eyes, hair and skin) abnormal behavior (this includes: hands flapping) short stature persistent hunger crossed eyes fascination with water

Causes It is a genetic mutation associated with the malfunction of the gene “ubiquitin protein ligase E3A (UBE3A)”. We usually get two copies of the UBE3A, one from each of our parents. In many of our tissues, both copies are activated, nevertheless in particular parts of the brain, only the maternal copy (that inherited from the mother) is activated. This is a result of “genomic imprinting”. There is more than one cause for the deletion/inactivation of this gene. This disease is usually caused by the deletion/absence of the maternal gene in the brain. Usually, it is because of the deletion, in chromosome 15, of a segment that has this gene. This is the case with 70% of those with the disease.   Another, less probable, cause is the malfunction/alteration of the maternal gene itself. This is the case with 15% of those with the disorder. Another, rare, cause is the inheritance of two copies of the gene from the father (this is called “paternal uniparental disomy”). This also associates with another possible cause, in which the maternal gene acts as if it came from the father (this is called "imprinting defect"). In addition, the cause of the disease, for some, can be unknown. This is the case with 10-15% of those with the disease.

Is it inherited? Usually: no, especially if it is caused by the deletion of the gene in the maternal chromosome 15, OR by paternal uniparental disomy ⇐ most of the time, they occur randomly...during gamete formation/early embryonic development ⇒ this disorder is not sex-linked. However, it is possible, but still very rare, that the genetic change that caused the disease could be passed on.

Treatment Unfortunately, we have not discovered a cure yet. The treatments currently available only target their developmental and medical problems. These include: - Anti-seizure medication - Physical therapy - Communication therapy - Behavior therapy Although gene therapy is supposed to be an option, scientists are still debating whether or not it would actually work. This is because the tests that they have carried out were on animals, and the difference in sizes of brain might be a vital factor.

Diagnosis If your doctor suspects that you have Angelman Syndrome, you would be asked for a blood sample. The following genetic tests could then be taken from that sample: - Chromosome analysis ⇐ to check for any chromosomal mutations - Fluorescence in situ hybridisation (FISH) ⇐ to check for any deletions in chromosome 15 - DNA methylation ⇐ to check if the genes on the parents’ chromosomes are active - UBE3A gene mutation analysis ⇐ to check for any mutations in the maternal copy of the gene

Genetic Counseling Although this disease is rarely passed on from one generation to the next, genetic counseling is still an option. This is to highlight any possible risks of passing on the genetic change.

Probability Approximately 1 in 1,600 people are diagnosed with Angelman Syndrome. It is equally common in males as it is in females.

Nancy Ashour Bibliography "Angelman Syndrome." Genetics Home Reference. U.S. National Library of Medicine, 1 June 2015. Web. 4 June 2015. "Angelman Syndrome." National Organization for Rare Diseases. NORD, 2015. Web. 6 June 2015. "Angelman Syndrome." NHS Choices. National Health Service, 2 Sept. 2014. Web. 4 June 2015. Hendrickson, Jill E. "Genetic Counseling for Angelman Syndrome." GeneticaLens. GeneticaLens, 2003. Web. 6 June 2015. Mayo Clinic Staff. "Angelman Syndrome." Mayo Clinic. Mayo Foundation for Medical Education and Research, 5 Dec. 2014. Web. 4 June 2015. Nall, Rachel. "What Causes Seizures? 77 Possible Conditions." Healthline. HealthReferenceLibrary, n.d. Web. 3 June 2015. "NINDS Angelman Syndrome Information Page." National Institution of Neurological Disorders and Stroke. National Institutes of Health, 7 Oct. 2011. Web. 3 June 2015. "What Is Prader-Willi Syndrome?" Prader-Willi Syndrome Association. Prader-Willi Syndrome Association, 2015. Web. 4 June 2015. Singer, Emily. "Gene Therapy." Simons Foundation Autism Research Initiative. Simons Foundation, 20