Angelman syndrome

Individuals with Angelman syndrome (AS) commonly have a happy, hyper-excitable disposition, and may have frequent bursts of laughter that are not associated with anything in particular . It is not known why laughter is so common in AS. Although babies with AS typically have developmental delays, persistent social smiling, giggling and chuckling are common. This happy, excitable nature is thought to contribute to sleep disorders, which are common in individuals with Angelman syndrome. Although this is a frequent trait of individuals with Angelman syndrome, like anyone, individuals with Angelman syndrome are not always happy, and some children Angelman syndrome are prone to bouts of irritability.

The Angelman Syndrome Foundation has regional representatives that can help connect you with other families in your area. You can find a link to these resources, and other resources the Angelman Syndrome Foundation provides at: http://www.angelman.org/resources-education/regional-representatives/.
The Angelman Syndrome Foundation holds annual Scientific Symposiums, as well as a biennial meeting for families, caregivers, educators, healthcare providers, and scientists to gather, collaborate, and share information about Angelman syndrome. You can learn more about this conference at: http://www.angelman.org/conferences-symposia/.
The Angelman Syndrome Support Education and Research Trust in the UK sponsors national and regional conferences for families and professionals working with Angelman syndrome to meet. You can learn more about this conference at:http://angelmanuk.org/events-and-conferences-for-angelman-syndrome-assert/

Individuals with Angelman syndrome are typically seen by several different specialists, including:

Angelman syndrome is most often abbreviated as AS.

Angelman syndrome is a genetic disorder that causes severe intellectual disabilities. Most individuals with Angelman syndrome do not speak, or use only a few words. Angelman syndrome affects the way that a person’s brain coordinates their movements, called ataxia. Ataxia can cause jerky movements and unsteady walking. Individuals with Angelman syndrome are often recognized as having a happy and excitable personality, with frequent bouts of laughter, smiling, hand-flapping or waving for no apparent reason. Most individuals with Angelman syndrome have a small head size, called microcephaly, as well as sleep disorders and seizures. There are a few facial features that are often seen in Angelman syndrome, including a prominent chin (prognathia), a protruding tongue, and a broad mouth with widely-spaced teeth, but in general, most individuals with Angelman syndrome resemble their families more than they resemble one another.

Individuals with Angelman syndrome are most likely to have the following health concerns:

A small protein called ubiquitin is known to play a role in neurologic development and neurologic disorders. In Angelman syndrome, a protein that interacts with ubiquitin, called ubiquitin ligase E3A (E6AP) is not produced. Normally, E6AP attaches ubiquitin to proteins that the body needs to break down, like a signal. This process is particularly important in the brain. When E6AP is not present or is not functional, this process does not work the way it is should, and proteins that would normally be broken down by the body are not.

It is not known exactly how this disruption to the protein breakdown process causes Angelman syndrome, although this is a topic of active research.

Angelman syndrome is caused by the lack of a protein called E6AP, that is made by a gene called ubiquitin-protein ligase E3A (UBE3A). The UBE3A gene is part of a group of genes that are imprinted. Typically, our bodies use both the maternally-inherited and paternally-inherited copy of our genes to make whatever that particular gene’s product is, like an enzyme or a protein. With imprinted genes however, one copy of the gene is switched on, and the other copy is switched off, based on which parent the gene was inherited from. With UBE3A, the maternally-inherited copy is "switched on", and makes UBE3A protein, while the paternally-inherited copy is "switched off" (imprinted) and does not make UBE3A protein.

There are four recognized types of genetic changes that can cause Angelman syndrome:

The most common features of Angelman syndrome include:

There is an online magazine dedicated to Angelman syndrome called "Angelman Today" at http://www.angelmantoday.com/.
The Foundation for Angelman Syndrome Therapeutics (FAST) at http://cureangelman.net/ is a fundraising organization whose mission is to fund a cure for Angelman syndrome. They have a Facebook page at https://www.facebook.com/www.cureangelman.org that allows families to post questions in an open forum and facilitates interaction with organizations and other families coping with Angelman syndrome.

Like most genetic disorders, there is presently no cure for Angelman syndrome. Individuals with Angelman syndrome benefit from treatment and management of common health concerns, including seizures, sleep disorders, movement disorders, speech impairment, intellectual disabilities, and hyperactivity. A variety of treatments, including physical therapy, speech & communication therapy, occupational therapy, and behavioral therapy can be used to help individuals with Angelman syndrome reach their full potential.

For more information about therapies, speak to your child’s doctor, and consider reaching out to family support groups, such as The Angelman Syndrome Foundation or the The Angelman Network.

Individuals with Angelman syndrome have a happy demeanor and often laugh or smile for no apparent reason. This happy disposition along with jerky movements, developmental disabilities, and little or no speech are characteristic of the disorder.

Angelman syndrome is not routinely tested for on state newborn screening. If there is a reason to suspect Angelman syndrome in the newborn period, genetic testing can be done. However, most children with Angelman syndrome do not begin to show symptoms until after one year of age.

The Angelman Syndrome Foundation has a list of research opportunities for interested families and individuals at: http://www.angelman.org/research/participate-in-research-studies/.
The Foundation for Angelman Syndrome Therapeutics maintains a list of research funded by their foundation with contact information for families interested in participating. You can see the list of these opportunities at: http://cureangelman.net/research/fast-funded-research/.
The Angelman Syndrome Support Education and Research Trust in the UK also maintains a list of research opportunities for families in the UK at: https://www.angelmanuk.org/research.

Hyperactivity is extremely common in children with Angelman syndrome. Children with Angelman syndrome have difficulty staying still and are often constantly in motion. Other behaviors, such as hyper-excitability and hand-flapping, appear to decrease with age. In childhood, impulse control, and unwanted behaviors such as grabbing, pinching and biting may be an issue, however behavior modification therapy can be helpful in these situations. Most children with Angelman syndrome do not require medication for their hyperactivity, however some children may benefit from this. Along with hyperactivity, a short attention span is quite common, however, this may also improve with age.

Angelman syndrome occurs in about 1 in 24,000 to 1 in 12,000 individuals. However, there may be more people with Angelman syndrome who have symptoms but have not been diagnosed.

Most of the genetic changes that cause Angelman syndrome happen randomly, during the formation of an egg or sperm, or very early during pregnancy. These changes are sporadic, meaning that they happen by chance. In this situation, the parents’ chance of having another child with Angelman syndrome is felt to be the same as that for the general population.

Very rarely, a genetic mutation in the UBE3A gene may be passed on from an unaffected parent to a child. In this situation, the chance of having another child with Angelman syndrome is as high as 50%.

If you are interested in setting up a local support group, you can reach out to the national and international support organizations listed below to see about creating a support group for your area. If you do begin a local support group, consider reaching out to Angelman syndrome specialty clinics to help get the word out to other families.

Many support group websites allow you to direct your donation to a specific cause, including research on Angelman syndrome. For example, on The Angelman Syndrome Foundation’s donation page, you can select "research" for your "area of giving.
The Foundation for Angelman Syndrome Therapeutics (FAST) is a group that funds research aimed at finding a cure for Angelman syndrome. You can donate to FAST at: http://cureangelman.net/others-ways-to-give/.
In addition to donating money, you can also explore creative ways of funding research through various Angelman Syndrome support organizations, such as purchasing items whose sales directly benefit the group. The Angelman Syndrome Support Education and Research Trust offers a number of ways to donate, as well as their "I’m No Angel" t-shirts, mugs, coffee cups and more at: http://458768.spreadshirt.co.uk/.

If you are concerned that your child may have Angelman syndrome, it is important to speak to your child’s doctor. Referral to a specialist, such as a geneticist, can be helpful to see whether your child’s symptoms fit with a clinical diagnosis of Angelman syndrome (i.e. a diagnosis based on physical, health, and developmental features). If Angelman syndrome is a possibility, a geneticist or genetic counselor can recommend which type of genetic testing would be most appropriate for your child based on his or her symptoms. It is possible that more than one type of genetic test will be required before the genetic diagnosis can be made. These tests are usually performed on a blood sample obtained from your child and include:

As of February 1, 2016, there are no centers of excellence in Angelman syndrome. However, the Angelman Syndrome Foundation has worked with specialists in Angelman syndrome to establish specialty clinics at locations in the United States so that many families with Angelman syndrome will have to travel no more than 4 hours to see a team of experts who treat Angelman syndrome. As of February 1, 2016, clinics are located at:

Speech and language problems are typical in Angelman syndrome (AS), and overall, most individuals do not speak, or have very limited speech. For this reason, gesturing, signing (including sign language) and assistive devices and technologies that employ the use of graphics, words, and symbols can be extremely beneficial. Children with AS often have a strong desire to interact with others, but if they have difficulty communicating, behavioral problems may arise. Helping facilitate communication between parents, family members, teachers, therapists, and peers allows for a better quality of life for individuals with AS.

The Angelman Syndrome Foundation has a page on their website dedicated to communication aids for individuals with AS at: http://www.angelman.org/resources-education/assistive-technology-aac/.

Reports from parents and studies of children with Angelman syndrome (AS) have identified common sleep disturbances, including night-time wakefulness and a decreased need for sleep. In fact, apart from seizures, sleep disturbances are one of the most frequently encountered issues. Consultation with a medical specialist is recommended to determine which treatment(s) may be most helpful. Parents have reported success with a number of techniques, including behavioral treatment, prescription sedatives, and a variety of homeopathic remedies.

While the typical features of Angelman syndrome include developmental delays, intellectual disabilities, severe speech impairment, ataxia (a movement disorder), seizures, microcephaly (small head), sleep disturbances, and hyperactivity, there are also a number of symptoms that are not seen in every person with Angelman syndrome. There are also some generalizations about the severity of certain features that can be made based on the type of genetic change the person has. (For information about the genetics of Angelman syndrome, please see the "Causes" section.)

Unlike conditions such as autism, which are thought to be the result of a combination of genetic and environmental factors, Angelman syndrome is a genetic disorder that is caused by the loss of function of a gene called UBE3A. Although the type of genetic change that causes UBE3A to not work have been correlated with mild differences in severity, there is no indication that environment plays a role in the severity of the major features of Angelman syndrome.

Some of the other medical conditions that are seen in individuals with Angelman syndrome, such as hyperactivity, hyperlocomotion, seizures, and sleep disorders may benefit from changes to the person’s physical and social environment to ensure maximum developmental ability, safety, and well-being. For suggestions on various types of therapies that have been used for individuals with Angelman syndrome, refer to the Therapy Services page of The Angelman Network.

Angelman syndrome was formerly known as happy puppet syndrome, due to a happy personality and an uncooordinated walk (ataxia), however, this term is no longer used. Angelman syndrome may also be known by its abbreviation, AS.

There are several support groups for families who have a loved one with a diagnosis of Angelman syndrome. As of June 1, 2016, support groups for Angelman syndrome include:

There are a number of disorders whose symptoms overlap with those seen in Angelman syndrome, including: