Angelman syndrome

Angelman syndrome is a rare genetic condition that affects the nervous system. It happens when the maternal UBE3A gene does not work as expected. This change leads to delayed development, trouble with speech, challenges with balance and movement, and intellectual disability. Seizures also are common.

Many children with Angelman syndrome smile or laugh often and appear easily excited. These behavior traits may be early clues for families and care teams.

Delays in maturing, called developmental delays, begin between about 6 and 12 months of age. The delays often are the first signs of Angelman syndrome. Seizures may begin between the ages of 2 and 3 years old.

People with Angelman syndrome tend to live close to a typical lifespan. But the condition can't be cured. Treatment focuses on supporting development, building communication skills, and managing medical, sleep and developmental issues.

Early signs of Angelman syndrome can be subtle at first, then become clearer as children grow. Angelman syndrome symptoms can affect development, movement, behavior and overall health. Symptoms may include:

• Seizures, often starting between ages 2 and 3.
• Small head size by age 2.
• Light-colored hair, skin or eyes.
• Tongue thrusting.
• Crossed eyes, called strabismus.
• Curved spine, called scoliosis.

Angelman syndrome symptoms often appear in clusters. These common categories help show how the condition can affect daily life:

Development and communication

• Developmental delays, including no crawling or babbling by 6 to 12 months.
• Intellectual disability.
• No speech or very limited speech.

Movement and balance

• Trouble walking, moving or balancing.
• Stiff or jerky movements.
• Movement patterns such as hand flapping or lifting the arms while walking.

Behavior

• Frequent smiling and laughing.
• Seeming very happy or easily excited.

Feeding and sleep

• Feeding challenges in babies, such as trouble sucking or taking a bottle.
• Trouble going to sleep and staying asleep.
• Frequent waking.

When to see a doctor

Most babies with Angelman syndrome don't show symptoms at birth. The first signs of Angelman syndrome most often are developmental delays. This includes lack of crawling or babbling between 6 and 12 months.

If your child seems to have developmental delays or if your child has other symptoms of Angelman syndrome, make an appointment with your child's healthcare professional.

Angelman syndrome is caused by changes in a gene, called a genetic change. It's most often caused by changes in a gene on chromosome 15 called the ubiquitin protein ligase E3A (UBE3A) gene.

A missing or damaged gene

You receive your pairs of genes from your parents. One copy comes from your mother, called the maternal copy. The other comes from your father, called the paternal copy.

Your cells most often use information from both copies. But in a small number of genes, such as the UBE3A gene, only the copy from the mother is active.

Most often, the maternal copy of the UBE3A gene helps the brain develop. Angelman syndrome happens when part of the maternal copy is missing or damaged. So the brain can't get the information it needs to develop and control speech and movement.

Rarely, Angelman syndrome is caused when two paternal copies of the gene are passed down instead of one from each parent.

How a child gets Angelman syndrome

• Think of each gene as an instruction card. For most genes, children get one instruction card from their mother and one from their father. The body usually reads both cards.
• But the UBE3A gene works differently in the brain. In the brain, only the mother's card is readable. The father's card is there, but it stays turned off.
• In Angelman syndrome, the mother's card is missing, damaged or unreadable. So the brain is left without instructions from UBE3A. Without those instructions, parts of brain development — such as movement, learning, speech and coordination — don't happen in the typical way.

All of these lead to the same problem: The brain doesn't receive the working UBE3A instructions it needs.

Angelman syndrome is rare. Researchers often don't know what causes the genetic changes that result in the disease. Most people with Angelman syndrome don't have a family history.

In rare situations, Angelman syndrome can be passed down from a parent. This happens when the parent carries a specific UBE3A gene change or an imprinting condition. In these families, the chance of having another child with Angelman syndrome may be higher. Not all types of genetic changes can be passed on. Only a few specific ones carry a higher recurrence risk.

Complications linked to Angelman syndrome include:

• Trouble feeding. Trouble sucking and swallowing together may cause feeding problems in infants. Your child's healthcare professional may suggest a high-calorie formula to help your baby gain weight.
• Hyperactivity. Children with Angelman syndrome often move quickly from one activity to another, have a short attention span, and keep their hands or a toy in their mouths. Hyperactivity often decreases with age. Medicine often isn't needed.
• Seizures. Most affected children experience recurrent seizures. They sometimes can be difficult to manage, requiring ongoing management with medicines.
• Dental problems and vision issues. These may include nearsightedness or crossed eyes.
• Sleep troubles. People with Angelman syndrome often have changes in their sleep-wake patterns. They may need less sleep than most people. Sleep troubles may improve with age. Medicine and behavior therapy may help.
• Curving of the spine, also called scoliosis. Some people with Angelman syndrome get a side-to-side spinal curve over time.
• Obesity. Obesity is common in older children with Angelman syndrome.

Rarely, Angelman syndrome may be passed from an affected parent to a child through changed genes. If you're concerned about a family history of Angelman syndrome or if you have a child with the condition, seek medical advice. Your healthcare professional or a genetic counselor can help you plan future pregnancies.

Genetic testing can help find the exact gene condition in a person. This is very important for knowing if it might happen again and for helping families plan future pregnancies.

Your child's healthcare professional may suspect Angelman syndrome if your child has developmental delays, talks little or not at all, or has other symptoms. Symptoms can include seizures, trouble with movement and balance, or a small head size.

Angelman syndrome can be hard to diagnose because it shares symptoms with other conditions and syndromes, such as autism spectrum disorder, cerebral palsy and other genetic differences.

Tests

A genetic test can usually confirm Angelman syndrome. This gene testing can find changes in a child's genes that indicate Angelman syndrome.

A mix of gene tests can show the changes linked to Angelman syndrome. These tests may review:

• Parental DNA pattern. This test, known as a DNA methylation test, screens for three of the four known gene changes that cause Angelman syndrome.
• Missing chromosomes. A chromosomal microarray (CMA) can show if parts of chromosomes are missing.

• Gene changes. Rarely, Angelman syndrome happens when a person's maternal copy of the UBE3A gene is active but changed. If results from a DNA methylation test are typical but your child still has features of Angelman syndrome, your child's healthcare professional may order a UBE3A gene sequencing test to look for a maternal change.

  Because of the link between Angelman syndrome and seizures, a healthcare professional also might do an electroencephalogram (EEG). An EEG measures the electrical activity of the brain.

There's no cure for Angelman syndrome. Research is looking at targeting specific genes, including ways to restore UBE3A activity in the brain. Current treatment focuses on managing symptoms and supporting development at every age.

A team of healthcare professionals from different areas works with you to manage your child's condition. Depending on your child's symptoms, treatment for Angelman syndrome may involve:

• Antiseizure medicine to help control seizures.
• Physical or occupational therapy to support walking, movement and daily activities.
• Communication and speech therapy, which may include sign language, picture communication or speech-generating devices.
• Behavior therapy to help with hyperactivity, short attention span and behavioral development.
• Medicines and sleep training to manage sleep issues.
• Diet changes and medicines to help with feeding troubles and constipation.

Finding out that your child has Angelman syndrome can be hard. You may not know what to expect. You may worry about whether you can care for your child's medical needs and developmental disabilities. There are resources that can help.

Work with a team

Find a team of healthcare professionals, including therapists, that you trust to help you make decisions about your child's care and treatment. These professionals also can help you find local resources.

Consider a support group

Being in touch with other families facing issues like yours may help you feel more connected. Ask your child's healthcare professional about local support groups and other helpful organizations.

Call your healthcare professional if your baby or child is not developing as expected or has other symptoms of Angelman syndrome. Your healthcare professional may then refer you to a doctor who specializes in conditions that affect the brain and nervous system, called a neurologist.

Here's some information to help you get ready for your appointment.

What you can do

• Write down symptoms you've seen in your child, and when they began.
• Bring baby books and other records of your child's development to the appointment. Photos and video recordings can be helpful.
• List your child's key medical information, including other conditions for which your child is being treated. List the names of medicines, vitamins and supplements your child takes, including doses.
• Ask a family member or friend to join you for your child's appointment. Someone who's with you can offer support and help you remember the information you're given.
• Write down questions to ask your healthcare professional.

Questions to ask include:

• What is likely causing my child's symptoms?
• Are there other possible causes for these symptoms?
• What tests does my child need?
• Should my child see a specialist?

Questions to ask a specialist include:

• Does my child have Angelman syndrome?
• What are the possible complications of this condition?
• What therapies are there?
• What treatment do you suggest?
• What is the long-term outlook for my child?
• Should my child or I be tested for the gene changes that are linked to this condition?
• What other specialists should my child see?
• How can I find other families who are coping with Angelman syndrome?

Be sure to ask all the questions you have.

What to expect from your doctor

A healthcare professional who sees your child for possible Angelman syndrome might ask:

• Does your child have trouble eating?
• Is your child reaching the expected, age-related physical milestones?
• Have you seen issues with balance or movement?
• Does your child laugh, smile or get excited more often than peers?
• Does your child have odd behaviors, such as hand flapping?
• Does your child communicate in words?
• How well does your child sleep?
• Has your child had seizures? If so, how often?
• Have any of your child's first-degree relatives, such as a parent or sibling, been diagnosed with Angelman syndrome?