Angelman syndrome | genetic disorder

DEFINITION

Angelman syndrome is a genetic disorder that causes developmental disabilities and neurological problems, such as difficulty speaking, balancing and walking and, in some cases, seizures. Frequent smiles and outbursts of laughter are common for people with Angelman syndrome, and many have happy, excitable personalities.

Angelman syndrome usually isn't detected until parents begin to notice developmental delays when a baby is about 6 to 12 months old. Seizures often begin when a child is between 2 and 3 years old.

People with Angelman syndrome tend to live a normal life span, but they may become less excitable with age. Other signs and symptoms remain. Treatment for Angelman syndrome focuses on managing the child's medical and developmental problems.

SYMPTOMS

Characteristic Angelman syndrome signs and symptoms include:

• Developmental delays, such as lack of crawling or babbling at 6 to 12 months, and intellectual disability 
• Lack of or minimal speech 
• Inability to walk, move or balance well (ataxia) 
• Trembling movement of arms and legs 
• Frequent smiling and laughter 
• Happy, excitable personality 

People who have Angelman syndrome may also have other signs and symptoms, including:

• Seizures, usually beginning between 2 and 3 years of age 
• Stiff or jerky movements 
• Small head size, with flatness in the back of the head (microbrachycephaly) 
• Crossing of the eyes (strabismus) 
• Tongue thrusting 
• Walking with arms up in the air 
• Light pigmentation in hair, skin and eyes (hypopigmentation) 

When to see a doctor

Most babies with Angelman syndrome don't show signs or symptoms of the disorder when they're born. The first signs of Angelman syndrome are usually developmental delays, such as lack of crawling or babbling, between 6 and 12 months.

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

CAUSES

Angelman syndrome is a genetic disorder. It's most often caused by problems with a gene located on chromosome 15 called the ubiquitin-protein ligase E3A (UBE3A) gene.

Genes are segments of DNA that provide the blueprints for all of your characteristics. You receive your genes, which occur in pairs, from your parents. One copy comes from your mother (maternal copy), and the other copy comes from your father (paternal copy).

A missing or defective gene

Both genes in a pair usually are active. This means that your cells use information from both the maternal copy and the paternal copy of each gene pair. But in a small number of genes, only one copy of a gene pair is active. The activity of each gene copy depends on whether it was passed from your mother or from your father. This parent-specific gene activity is called imprinting. In these genes, when the copy that's usually active is missing or defective, it causes problems in the functions and characteristics controlled by that gene. 

Normally, only the maternal copy of the UBE3A gene is active in the brain, caused by what's known as genomic imprinting. Most cases of Angelman syndrome occur when part of the maternal chromosome 15, which contains this gene, is missing or damaged. In a small number of cases, Angelman syndrome is caused when two paternal copies of the gene are inherited, instead of one paternal and one maternal copy (paternal uniparental disomy). 

RISK FACTORS

Angelman syndrome is rare. In most cases, researchers don't know what causes the genetic changes that result in Angelman syndrome. Most people with Angelman syndrome don't have a family history of the disease. In a small percentage of cases, however, Angelman syndrome may be inherited from a parent, so a family history of the disease may increase a baby's risk of developing Angelman syndrome.

COMPLICATIONS

Complications associated with Angelman syndrome include:

• Feeding difficulties. Some infants with Angelman syndrome have problems feeding during the first few months of life because of an inability to coordinate sucking and swallowing. If your child has difficulty feeding, your pediatrician may recommend a high-calorie formula to help your baby gain weight. 
• Hyperactivity. Many young children with Angelman syndrome have increased motor activity. They may move quickly from one activity to another, often keeping their hands or a toy in their mouths. Their attention span may be very short. Hyperactivity often decreases with age in children with Angelman syndrome, and medication usually isn't necessary. 
• Sleep disorders. It's common for people with Angelman syndrome to have abnormal sleep-wake patterns and to need less sleep than normal. In some cases, sleep difficulties may improve with age. Medication and behavior therapy may help control sleep disorders. 
• Curving of the spine (scoliosis). Some people with Angelman syndrome develop this abnormal side-to-side spinal curvature over time. 
• Obesity. Older children with Angelman syndrome tend to have large appetites, which lead to obesity. 

PREPARING FOR YOUR APPOINTMENT

Call your doctor if your baby or child isn't reaching expected developmental milestones or has any other signs or symptoms common to Angelman syndrome. After your initial appointment, you may be referred to a doctor who specializes in the diagnosis and treatment of conditions that affect the brain and nervous system (neurologist).

Here's some information to help you get ready for your appointment and to know what to expect from your doctor.

What you can do

• Write down any signs or symptoms you've noticed in your child, and for how long. 
• Bring baby books and other records of your child's development. Photographs and video recordings can be helpful. 
• Make a list of your child's key medical information, including other conditions for which your child is being treated and the names of any medications, vitamins or supplements that he or she is taking. 
• Ask a trusted family member or friend to join you for your child's appointment. If your child's doctor mentions the possibility of a developmental disorder, you may have great difficulty focusing on anything the doctor says next. Take someone along who can offer emotional support and can help you take in all the information. 
• Write down questions to ask your doctor. Creating your list of questions in advance can help you make the most of your time with your doctor. 

Questions to ask your child's doctor at the initial appointment include:

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

Questions to ask if you're referred to a specialist include:

• Does my child have Angelman syndrome? 
• What are the possible complications of this condition? 
• What therapies are available for this condition? 
• What treatment approach do you recommend? 
• What is the long-term outlook for my child? 
• What is the developmental potential for a person with Angelman syndrome? 
• How often will you see my child to monitor his or her ongoing health and development? 
• Are my other children or family members at increased risk of this condition? 
• Should I or my child be tested for the genetic mutations associated with this condition? 
• What other types of specialists should my child see? 
• How can I find other families who are coping with Angelman syndrome? 

Don't hesitate to ask any other questions that occur to you.

What to expect from your doctor

A doctor who sees your child for possible Angelman syndrome is likely to ask you a number of questions. Being ready to answer them may reserve time to go over any points you want to talk about in-depth. The doctor may ask:

• What are your child's signs and symptoms? 
• When did you first notice these signs and symptoms? 
• Is your child having problems with nursing or feeding? 
• Is your child reaching the physical milestones that are expected for his or her age? 
• Have you noticed any problems with balance, coordination or movement that seem unusual compared with your child's peers? 
• Does your child seem to laugh, smile or express excitement more often than his or her peers? 
• Does your child express excitement with unusual physical behaviors, such as flapping his or her hands? 
• Does your child communicate verbally, either with babbling or cooing or — in older babies and children — with words? 
• Does your child have a normal daily rhythm of sleeping and waking? 
• Has your child had any 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? 
• Do you have support from a partner or family to help with a child with special needs? 

TESTS AND DIAGNOSIS

Your child's doctor may suspect Angelman syndrome if your child has developmental delays and other signs and symptoms of the disorder, such as problems with movement and balance, small head size, and flatness in the back of the head, along with frequent laughter.

Confirming a diagnosis of Angelman syndrome requires taking a blood sample from your child for genetic studies. A combination of genetic tests can reveal the chromosome defects related to Angelman syndrome. These tests may look at:

• Chromosome size, shape and number.This test, known as chromosome analysis (karyotyping), examines chromosomes in a cell sample. 
• Missing chromosomes. Known as fluorescence in situ hybridization (FISH), this test can show if portions of any chromosomes are missing. 
• Parental DNA pattern. This test, known as a DNA methylation test, reveals a gene's imprinting pattern. Normal results show both a paternal and maternal DNA pattern — meaning genes from both parents are active. In some areas of the brain, only the maternal gene is active. In most cases for people with Angelman syndrome, the maternal copy of the gene is lost, so there are no copies of the gene operating in the brain. 
• Gene mutation. Rarely, Angelman syndrome may occur when a person's maternal copy of the UBE3A gene is active, but mutated. If results from a DNA methylation test are normal, your child's doctor may order a UBE3A gene sequencing test to look for a maternal mutation. 

TREATMENTS AND DRUGS

Because there isn't a way to repair chromosome defects, there's no cure for Angelman syndrome. Treatment focuses on managing the medical and developmental problems that the chromosome defects cause.

A team of health care professionals will likely work with you to manage your child's condition. Depending on your child's signs and symptoms, treatment for Angelman syndrome may involve the following:

• Anti-seizure medication. Medication may be necessary to control seizures caused by Angelman syndrome. 
• Physical therapy. Children with Angelman syndrome may learn to walk better and overcome other movement problems with the help of physical therapy. 
• Communication therapy. Although people with Angelman syndrome usually don't develop verbal language beyond simple sentences, communication therapy can be helpful. Nonverbal language skills may be developed through sign language and picture communication. 
• Behavior therapy. Behavior therapy can help children with Angelman syndrome overcome hyperactivity and a short attention span, which can aid in developmental progress. Although the level of development people with Angelman syndrome can achieve varies widely, many are outgoing and are able to build relationships with friends and family. 

LIFESTYLE AND HOME REMEDIES

Angelman syndrome is a genetic disorder that causes developmental disabilities and neurological problems, such as difficulty speaking, balancing and walking and, in some cases, seizures. Frequent smiles and outbursts of laughter are common for people with Angelman syndrome, and many have happy, excitable personalities.

Angelman syndrome usually isn't detected until parents begin to notice developmental delays when a baby is about 6 to 12 months old. Seizures often begin when a child is between 2 and 3 years old. 

People with Angelman syndrome tend to live a normal life span, but they may become less excitable with age. Other signs and symptoms remain. Treatment for Angelman syndrome focuses on managing the child's medical and developmental problems.