Angelman syndrome

A person with Angelman syndrome will have a near-normal life expectancy, but needs looking after for the rest of their life.

Characteristics of Angelman syndrome

The typical characteristics of Angelman syndrome aren't usually apparent at birth.

A child with Angelman syndrome will begin to show signs of delayed development at around 6-12 months, such as being unable to sit unsupported or make babbling noises.

Later, they may not speak at all or may only be able to say a few words. However, most children with Angelman syndrome will be able to communicate using gestures, signs or other systems.

The movement of a child with Angelman syndrome will also be affected. They may have difficulty walking because of problems with balance and co-ordination ( ataxia ). Their arms may tremble or move jerkily, and their legs may be stiffer than normal.

A number of distinctive behaviours are associated with Angelman syndrome. These include:

• frequent laughter and smiling, often with little stimulus
• being easily excitable, often flapping the hands
• being restless (hyperactive)
• having a short attention span
• problems sleeping and needing less sleep than other children
• a particular fascination with water

By around two years of age, an abnormally small head which is flat at the back (microbrachycephaly) will be noticeable in some children with Angelman syndrome. Children with Angelman syndrome may also start to have seizures (fits) around this age.

Other possible features of the syndrome include:

• tendency to stick the tongue out
• crossed eyes (strabismus)
• pale skin, and light-coloured hair and eyes in some children
• a wide mouth with widely spaced teeth
• a side-to-side curvature of the spine ( scoliosis )
• walking with arms in the air

Some young babies with Angelman syndrome may have problems feeding because they're unable to co-ordinate sucking and swallowing. In such cases, a high-calorie formula may be recommended to help the baby gain weight. Babies with Angelman syndrome may need to be treated for reflux.

Causes of Angelman syndrome

In most cases of Angelman syndrome, the child's parents don't have the condition and the genetic difference responsible for the syndrome occurs by chance around the time of conception.

The typical characteristics of Angelman syndrome are caused when the Angelman gene, known as UBE3A, is either absent or malfunctions. A gene is a single unit of genetic material (DNA) which acts as an instruction for the way an individual is made and develops.

A child usually inherits one copy of the UBE3A gene from each parent. Both copies are switched on (active) in most of the body's tissues. However, in certain areas of the brain, only the gene inherited from the mother is active.

In most cases of Angelman syndrome (about 70%), the child's maternal copy of the UBE3A gene is missing (deleted), which means there's no active copy of the UBE3A gene in the child's brain.

In around 11% of cases, the maternal copy of the UBE3A gene is present but altered (mutated).

In a small number of cases, Angelman syndrome occurs when a child inherits two copies of chromosome 15 from the father, rather than inheriting one from each parent. This is known as uniparental disomy.

It can also occur when the copy of the UBE3A gene that comes from the mother behaves like it came from the father. This is known as an "imprinting defect".

In about 5-10% of cases, the cause of Angelman syndrome is unknown. Most children in these unexplained cases have different conditions involving other genes or chromosomes.

Diagnosing Angelman syndrome

Angelman syndrome may be suspected if a child's development is delayed and they have the syndrome's distinctive characteristics (see above).

A blood sample can be taken to confirm the diagnosis. A number of genetic tests will be carried out on the sample. These may include:

• chromosome analysis – to see if any parts of the chromosomes are missing (deletions)
• fluorescence in situ hybridisation (FISH) – used to check specifically for chromosome 15 deletions when Angelman syndrome is suspected, or to check the mother's chromosomes
• DNA methylation – which shows whether the genetic material on both the mother's and father's chromosomes is active
• UBE3A gene mutation analysis – used to see if the genetic code on the maternal copy of the UBE3A gene is altered

For each child with Angelman syndrome, it's important to know the genetic change that caused the condition. This helps to determine whether there's a risk of it occurring again in another child, or whether there are implications for other members of the family.

Most children with Angelman syndrome are diagnosed between the ages of 18 months and 6 years, when the typical physical and behavioural symptoms become apparent.

If your child is diagnosed with Angelman syndrome, you should be given the opportunity to discuss the genetic diagnosis and implications with a genetic doctor.

Managing Angelman syndrome

Some of the symptoms of Angelman syndrome can be difficult to manage, and you're likely to need help from a wide range of different healthcare professionals.

Your child may benefit from some of the following treatments and aids:

• anti-epileptic medicine to control the seizures – sodium valproate and clonazepam are some of the most commonly prescribed medicines and ketogenic diets have also been used
• physiotherapy may help to improve posture, balance and walking ability; it's also important to prevent permanent stiffening (contractures) of the joints as people with Angelman syndrome get older
• a back brace or spinal surgery may be recommended to prevent the spine from becoming more curved (see treating scoliosis )
• an ankle or foot orthosis (lower leg brace) may be recommended to help with walking independently
• communication therapy may be needed to help them develop non-verbal language skills, such as sign language and using visual aids; using iPad applications and similar tablet devices may also help
• behavioural therapy may be recommended to help overcome problem behaviours, hyperactivity and a short attention span
• activities such as swimming, horseriding and music therapy have also been reported as being beneficial

While there's currently no cure for Angelman syndrome, the results of preliminary genetic research have been promising. Following these studies, scientists believe it may be possible to restore UBE3A function in the brains of people with Angelman syndrome at some stage in the future.

There are also clinical trials looking at treatment for some of the symptoms associated with Angelman syndrome, such as treatments for seizures.

With age, people with Angelman syndrome become less hyperactive and the sleeping problems tend to improve. Most people with the syndrome will have intellectual disability and limited speech throughout their life.

In later childhood, the seizures usually improve, although they may return in adulthood. In adults, some mobility may be lost and joints may stiffen up. People with Angelman syndrome usually have good general health, are often able to improve their communication and acquire new skills throughout their lives.