Angelman Syndrome

Angelman syndrome is a complex genetic disorder that causes developmental and neurological problems, such as severe speech impairment and trouble walking and balancing (ataxia).

• Affects about 1 in 10,000 people
• People with Angelman syndrome are usually happy and affectionate and may laugh often and at inappropriate times
• Affected people may also have epilepsy
• Is often associated with low levels of pigment in skin, hair, and eyes
• Treatment focuses on the behaviors associated with the disorder

There are no known risk factors for Angelman syndrome. In some cases a family history may increase the chances of a baby having the disorder, but the disease is rare. If you already have a child with Angelman syndrome or are concerned about a family history, talking with your doctor or a genetic counselor may be helpful.

Children with Angelman syndrome may have feeding difficulties, sleep problems, and hyperactivity.

• Feeding difficulties, such as problems sucking and swallowing, may occur during the first few months of life.
• Sleep disorders, such as frequent waking, may need to be treated with medication or behavior therapy.
• Hyperactivity tends to decrease as children get older, but many young children with Angelman syndrome may have short attention spans and move quickly from one activity to the next.

• Hand flapping or walking with arms in the air
• Jerky body movements
• Stiffed-leg walk
• Little or no speech
• Attention deficits and hyperactivity
• Feeding problems, especially in infancy
• Sleep problems and a need for less sleep than their peers
• Delays in motor development
• Frequent laughter that may occur at inappropriate times
• Excitable personality
• Tongue thrusting
• Strabismus (crossing of the eyes)
• Small head size with flatness in the back of the head
• A lower jaw that juts out
• Light pigmentation in the hair skin and eyes

Angelman syndrome is caused by a genetic mutation on chromosome 15. The name of this gene is UBE3A. Normally, people inherit one copy of the gene from each parent, and both copies become active in many areas in the body. Angelman syndrome occurs when only one copy of the gene is active in certain areas of the brain.

There are no signs of Angelman syndrome at birth. The disorder is typically diagnosed at ages 6 to 12 months, when parents begin to notice developmental days such as a lack of crawling or babbling. Seizures may begin at ages 2 to 3. A doctor may suspect the disorder in children who have some of these symptoms in addition to others, such as difficulty with movement and balance, a small head size with flatness in the back, and frequent laughter.

To confirm a diagnosis of Angelman syndrome, your child's doctor will perform a combination of genetic tests that can include the following:

• Chromosome analysis to examine the size, shape, and number of chromosomes in a cell
• Fluorescent in situ hybridization (FISH) to see if any chromosomes are missing
• DNA methylation test to see if both copies of a gene — one from the mother and one from the father — are active
• Sequencing of the ubiquitin-protein ligase E3A (UBE3A): to look for a mutation in the maternal mutation of this gene, which is a rare cause of Angelman syndrome

Treatment for Angelman syndrome focuses on managing the child's medical problems and developmental delays since there is no cure to repair chromosomes. Treatment may include the following:

• Anticonvulsant medication for seizures
• Physical therapy to help with joint mobility and movement
• Speech therapy
• Occupational therapy
• Behavior therapy

People with Angelman syndrome have almost normal life spans. Adults are not usually able to live on their own but can learn basic household tasks and can live in group homes. Some individuals can have jobs in which they are supervised directly.

Researchers are studying children with Angelman syndrome to determine the highest dose of a new class of drugs called antisense oligonucleotides (ASOs) that can be given without causing serious side effects. It is thought that these drugs can help control some of the neurological and movement difficulties associated with the disorder, such as tremors.

An ongoing Angelman syndrome Natural History Study seeks to improve our understanding of how development, behavior, and communication change in individuals with AS over the course of their lives.