What Is Angelman Syndrome?

Symptoms can differ and affect people differently. People with Angelman syndrome frequently smile and laugh and have happy, excitable personalities. Angelman syndrome usually manifests itself as developmental delays between the ages of 6 and 12 months. Seizures can start between two and three years.

Early signs and symptoms of Angelman syndrome

• Feeding problems
• Delayed milestones
• Unusual movements, including fine tremors and jerky limb movements
• Epilepsy
• Lack of speech development and baby babble
• Poor sleep patterns
• Happy demeanor
• Hand flapping, especially when excited
• Low muscle tone

Later signs and symptoms of Angelman syndrome

• Flattened back of the head
• Light skin and hair color (compared with those of other family members)
• Tendency to chew objects
• Severe learning and physical difficulties
• Tendency to laugh a great deal

Consistent features seen in all people with Angelman syndrome

• Developmental delay
• Speech impairment, minimal or no use of words but nonverbal communication skills are higher
• Significant limitations both in intellectual functioning and adaptive skills (social skills and activities of daily living)
• Ataxia (balance disorder)
• Frequent laughter
• Easily excitable with hand-flapping movements
• Short attention span

Frequent features seen in 80 to 99 percent of people with Angelman syndrome

• Microcephaly (smallness of head circumference)
• Seizures
• Abnormal electroencephalogram

Associated features seen in 20 to 80 percent of people with Angelman syndrome

• Protruding tongue
• Swallowing disorders
• Hypopigmented skin and eyes (light-colored)
• Wide mouth and wide-spaced teeth
• Sleep disorders
• Fascination to water
• Increased sensitivity to heat
• Uplifted, flexed arms during walking
• Frequent drooling
• Strabismus (crossed eyes)
• Scoliosis (curved spine)
• Trouble feeding
• Heartburn (acid reflux)
• Unusual chewing and mouthing movements
• Crossed eyes

According to a recent study, approximately half of people with Angelman syndrome will have autism spectrum disorder. Make an appointment with a doctor if your child appears to have developmental delays or other signs or symptoms of Angelman syndrome.

Angelman syndrome is caused by the mutation or complete deletion of a specific gene on a chromosome. Researchers are still debating why this happens.

Recent research and studies have revealed the following causes:

• UBE3A gene
  • An abnormality in the UBE3A gene causes Angelman syndrome. This gene helps produce an enzyme called ubiquitin protein ligase E3A. 
  • This enzyme ensures normal neurological development by regulating the accumulation of potentially harmful proteins in the nervous system.
  • When ubiquitin-protein ligase production is hampered, it results in abnormal neurological development.
  • In some cases, abnormalities in the UBE3A gene are inherited, whereas, in others, damage to the gene appears to occur spontaneously during fetal development. In approximately 10 percent of cases, the cause of the disorder is unknown.
• Genes on chromosome 15
  • An error in one of the genes on chromosome 15 causes Angelman syndrome. There are several different ways in which this gene can be affected, including:
    • In 75 percent of cases: A missing piece of genetic material (deletion) on one of the chromosomes (most common cause).
    • In 10 percent of cases: Alteration in the Angelman gene.
    • In 3 percent of cases (uniparental disomy): One inherits both copies of chromosome 15 from their father. Typically, one copy of chromosome 15 is inherited from the mother, and one copy from the father.
    • In 2 percent of cases: Inheriting a “switched off” copy of the Angelman gene from the mother.
• Imprinting defect
  • It can occur when the copy of a gene from the mother behaves as it came from the father.

The cause of Angelman syndrome is unknown in about 5 to 10 percent of cases. Most children in these unexplained cases have other conditions involving other genes or chromosomes.

Angelman syndrome is uncommon. Most people with Angelman syndrome do not have a history of the condition in their families. Rarely, a parent may pass on Angelman syndrome to their child. A family history of this condition may increase an infant's risk of Angelman syndrome.

If you have a child with Angelman syndrome, the chances of having another afflicted child are low (about one percent). However, in a few families, the risk could be higher.

Angelman syndrome is diagnosed by a neurologist. A child should be investigated for Angelman syndrome if their development is delayed and they exhibit the disease's hallmark symptoms.

To confirm the diagnosis, a blood sample might be collected. The sample will be subjected to several genetic tests. These might include:

• Chromosome analysis: Identifies whether any chromosomes are missing (deletions).
• Fluorescence in situ hybridization: Looks for chromosome 15 deletions or the mother's inherited chromosomes.
• DNA methylation: Determines whether the inherited genetic material on the mother's and father's chromosomes is active.
• UBE3A gene mutation analysis: Examines whether the genetic code on the maternal copy of the UBE3A gene has been altered.

Other tests

• MRI: Identifies changes in the child's brain.
• Electroencephalogram: Determine where in the brain the seizures are coming from (if they are having seizures).

Angelman syndrome’s symptoms are present in approximately 10 percent of cases without the known associated genetic abnormalities. Genetic testing may not diagnose the disorder in these cases.

It is critical to identify the genetic change that caused Angelman syndrome in each child. This helps determine whether there is a risk of it happening again in another child or are any implications for other family members.

Angelman syndrome has no known cure. Treatment programs can help relieve symptoms, prevent secondary complications, and enhance the effects of symptoms.

Goals of managing people with Angelman syndrome

• Mitigate gross and fine motor delays
• Improve communication with nonverbal methods
• Intervention for autism spectrum disorder when present

Support for children and families

• Diagnosis and access to a supporting team
• Genetic counseling and testing
• Recognition and management of epilepsy if present
• Management of hyperactivity
• Discuss possible therapies and family support

To alleviate physical symptoms, medications or therapies could be prescribed. Symptoms of Angelman syndrome that may respond to treatment are:

• Seizures
• Constipation
• Gastroesophageal reflux
• Strabismus (crossed eyes)
• Sleeplessness
• Feeding problems

A multidisciplinary team of healthcare professionals will likely work together to manage the child's condition.

Angelman syndrome is commonly treated with the following therapies:

• Physical therapy
• Speech and communication therapies
• Occupational therapy
• Behavioral therapies

Physical and occupational therapies to improve adaptive functioning and speech therapy emphasizing nonverbal communication methods are available. Individualized and adaptable instructional curricula are required for school-aged children.

Other treatments include:

• Surgery
  • Reflux symptoms may necessitate fundoplication (a surgical technique used to treat acid reflux in the stomach). Specific orthopedic problems may necessitate surgery.
• Nutrition and diet
  • Changes in diet can help with gastrointestinal issues.
  • Studies report that a high-fat, low-carbohydrate diet (the ketogenic diet) might help some people.
• Coping and support
  • It can be challenging to learn that your child has Angelman syndrome. You might be unsure what to expect. There are resources available to assist.
  • Consider joining a support group. Connecting with other families dealing with similar issues may give you hope. Inquire with your doctor about local support groups and other helpful organizations.
• Clinical trials
  • Targeting particular genes for treatment is the focus of current research. Although there is currently no treatment for Angelman syndrome, early genetic research has yielded encouraging results.
  • Researchers are looking into the syndrome's genetic, cellular, and molecular causes to develop gene therapy techniques. Other studies aim to lessen the cognitive deficits associated with Angelman syndrome.
  • These studies have led researchers to speculate that, in the future, it could be possible to reactivate the UBE3A gene in the brains of those with Angelman syndrome. 
  • Clinical trials are underway to treat some Angelman syndrome symptoms, including seizure treatments.

Early diagnosis and tailored interventions and therapies help improve quality of life. Special education services are extremely beneficial for children with Angelman syndrome. Early speech, physical, and occupational therapies improve their communication and gross and fine motor skills.

• Better nonverbal communication skills: Although most people with Angelman syndrome will have severe developmental delays, speech impairments, and motor difficulties, they understand most of what is said and frequently pick up nonverbal communication skills and the use of assistive technology.
• Genes: Those without gene deletions typically make more developmental progress and have better communication skills. Gene deletions affect people more severely.
• Normal lifespan: People with Angelman syndrome seem to live normal lives and typically do not experience developmental regression as they age. Seizures improve or resolve for most people when they enter adolescence and adulthood, sleep improves but remains a problem for many and gastrointestinal symptoms do not change significantly over time.
• Post puberty: Anxiety tends to get worse and can cause problematic behaviors. Myoclonus, a common twitching in the hands that can affect the arms and the rest of the body, affects many adolescents and adults with Angelman syndrome. Although myoclonus is not a seizure activity, it can affect the quality of life and may require medication.
• Adulthood:
  • Their hyperactivity decreases and sleep patterns improve. Many children with Angelman syndrome grow up to be able to live in adult community homes with limited independence.
  • Many have friendships and interact socially.
  • Treatment helps improve function.
  • People with Angelman syndrome cannot live by themselves. However, they may learn certain tasks and live with others in a supervised setting.