Angelman Syndrome
Definition
Angelman (pronounced angel-man) syndrome, also known as AS, is a neurogenetic disorder that causes difficulty with movement and balance, seizures, developmental delay, and severe speech impairment. Angelman syndrome is rare, occurring in only one out of 15,000 live births with about 500,000 people living with the disorder across the globe. (Angelman Syndrome Foundation) Angelman syndrome was first identified in 1965 by Dr Harry Angelman of England and it is difficult to diagnose at birth, with most children being diagnosed between the ages of 1 to 4. The most common early sign that a child may have Angelman syndrome is “jerky movements due to an inability to coordinate voluntary movements” (NORD). Another common symptom of Angelman syndrome is children is holding “their arms up with the wrists and elbows bent and may flap their hands repeatedly when walking or excited” (NORD). Along with these repeated hand movements, children with Angelman syndrome also have frequent spans of laughing, smiling, and hyperactivity often unprovoked and over prolonged periods of time. Due to the jerky movements that many children with Angelman syndrome have, their motor milestones may be delayed with many children not walking until age 2 or 3, and a smaller amount not gaining the skill until 5 to 10 years of age. Based on these symptoms, Angelman syndrome is often misdiagnosed as Autism or Cerebral Palsy. Children with Angelman syndrome also often have delayed growth in head circumference which usually results in microcephaly (circumference of head is smaller than normal) by two years of age. Less common symptoms include frequent drooling, abnormal sleep-wake cycles, wide mouth with wide spaced teeth, and hypopigmented skin, light hair and light eye color compared to that of their family.
Causes and Types of Angelman Syndrome
The failure to function of a maternally inherited (from mother) gene is the cause of Angelman syndrome. The gene is called UEB3A and it is located in the 15th maternal chromosome. In typically developing children, the UEB3A paternal gene is silenced in the brain and the maternal copy of the gene is at work. In children with Angelman syndrome, the maternal UEB3A gene is not working and that interferes with the body’s messenger mRNA from working properly. The Foundation for Angelman Syndrome Therapeutics describes mRNA as the the “FedEx of the body”. They go on to say “Our DNA uses mRNA as a delivery service to send blueprints to the protein-assembly factories of our cells. People with AS have a mutation, deletion or other defect in their UBE3A gene that interrupts this delivery service. As a result, their neurons do not make any functional UBE3A protein, and that’s what triggers the symptoms of AS”. Therefore, a mutation of the UBE3A protein is responsible for all symptoms of Angelman syndrome.
There are four different types of Angelman Syndrome. The chart below from The Foundation for Angelman Syndrome Therapeutics shows the different impacted portions of the gene and how they often they occur in cases of Angelman syndrome.
Instructional Strategies
Imprinting Defect (<3%)
The imprinting center is a small stretch of DNA located in the q11-13 region of the chromosome. In rare cases, the mother’s chromosome 15 is blank, and the center copies the father’s chromosome 15. This is an imprinting defect.
Deletion (65-75%)
DNA (deoxyribonucleic acid) is the main component of chromosomes. It contains our unique genetic code. Most individuals with AS are missing a piece of DNA in region 15q11-13 on the maternal chromosome 15.
Uniparental Disomy (3-7%)
An individual with UPD has two copies of chromosome 15 from their father, instead of one each from the father and mother. UPD usually happens if there is no chromosome 15 in the egg.
Mutation (5-11%)
This occurs when there is a small abnormality in the DNA of the UBE3A gene. A mutation can happen anywhere on the gene.
Children with Angelman syndrome often have severe speech impairments, and there are many things that educators can do to create a positive learning environment for these students. The Genetics Education Materials for School Success says that teaching learning strategies for non-verbal expression is extremely important. They suggest using a manually signed system such as American Sign Language to bridge communication. Some children with Angelman may also benefit from communication boards or picture cards to create conversation. Those with severe motor impairments may benefit from an Augmentative and Alternative Communication (AAC) device to help communicate. Students with Angelman syndrome would benefit from speech therapy to help with communication needs. Students would also benefit from physical therapy and occupational therapy services to help with use of hands and to promote walking.
Useful Websites
https://www.angelman.org/ Angelman Syndrome Foundation
https://ghr.nlm.nih.gov/condition/angelman-syndrome#diagnosis US National Library of Medicine
https://rarediseases.org/rare-diseases/angelman-syndrome/ National Organization for Rare Disorders
https://cureangelman.org/ Foundation for Angelman Syndrome Therapeutics
https://www.angelmanuk.org/ Angelman Syndrome Support Education & Research Trust
Research
https://news.brown.edu/articles/2013/02/angelman
Professors from Brown University in Boston have created a compound in a study of Angelman using mice that may help to restore brain function depleted by the syndrome.
The Angelman Syndrome Foundation awarded the lab of Dr Mark Zylka of The University of North Carolina Chapel Hill $200,000 in 2018 to examine gene-editing technology as a possible cure for Angelman Syndrome.
https://today.uconn.edu/2017/04/isolating-their-target/#
Eric Levine, neuroscientist at the University of Connecticut studies the electrical activity of brain cells in neurons that occur as early as fetal development. No other study has backtracked this far to find early signs of Angelman.