Angelman Syndrome

Angelman syndrome is a genetic disorder that affects the nervous system and causes severe physical and intellectual disability.

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

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.

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.