Angelman syndrome

Angelman syndrome is a genetic condition that is present at birth (congenital). Most cases occur when a particular gene, the UBE3A gene on chromosome 15, is missing (a deletion). Other causes include the UBE3A gene being incorrectly inactivated, or a change (mutation) in the gene.

Characteristics of Angelman syndrome include distinctive facial features, intellectual disability, speech problems, a jerky walking style, a happy demeanour and hyperactive behaviour. The condition was once known as “happy puppet syndrome” because of the child’s sunny outlook and jerky movements. It is now named after Harry Angelman, the doctor who first investigated the symptoms in 1965.

Most diagnoses are made between the ages of two and five years. Estimates vary, but Angelman syndrome is thought to affect about one child in every 10,000 to 20,000.

Symptoms#

Symptoms that are usually present include:

• delayed motor development, such as delays in sitting, crawling and walking
• speech problems, or no speech at all
• problems with balance and coordination (ataxia)
• jerky, puppet-like movements and a stiff-legged walking style
• hand flapping and hyperactive behaviour
• a loving, happy and social demeanour, and a child easily moved to laughter
• intellectual disability, with delayed development in all areas, usually severe
• a small head (microcephaly) and characteristic brainwave abnormalities

Symptoms that are sometimes present include epilepsy, which occurs in more than 80% of cases. The characteristic physical features are not always obvious at birth but develop during childhood.

Physical characteristics#

• a flattened back of the head (microbrachycephaly)
• deep-set eyes
• a wide, ever-smiling mouth
• a prominent jaw and widely spaced teeth
• lightly pigmented hair, skin and eyes

Behaviour-related problems#

Common problems can include a very short attention span, feeding difficulties, disturbed sleep, and delayed toilet training (about 80% of adults are dry during the day).

Causes#

A child inherits two sets of chromosomes, one from each parent, and so usually inherits one copy of the UBE3A gene on chromosome 15 from each parent. Both copies are active in many parts of the body, but in some areas of the brain only the copy inherited from the mother is active. This is normal.

If this maternal gene is missing, or there is a change or mutation in it, the person has no working copy of the gene in those parts of the brain. As a result, they do not have enough UBE3A protein in the brain, which is thought to be what causes Angelman syndrome.

The main causes can be summarised as follows:

• A section of genetic material that usually contains the UBE3A gene is missing from the copy of chromosome 15 inherited from the mother (around 68% of cases). The mother’s chromosome 15 is normal; the genetic material is lost during the development of the egg.
• A change (mutation) in the UBE3A gene on chromosome 15 prevents its expression or function (around 11% of cases).
• The child inherits two copies of chromosome 15 from the father (around 7% of cases). Because the maternal copy is normally needed for proper expression of UBE3A, there are not normal levels of the protein in the brain.
• The child has a deletion elsewhere on chromosome 15 that leads to loss of expression of the mother’s UBE3A gene (around 3% of cases).
• In about 11% of cases, the cause is not known.

Diagnosis#

Diagnosis involves checking for the clinical features of Angelman syndrome and carrying out DNA tests. The condition may be mistaken for autism because of similar symptoms, including hyperactive behaviour, speech problems and hand flapping. However, a child with Angelman syndrome is highly sociable, unlike a child with autism. Careful diagnosis is important, because sometimes Angelman syndrome and autism are both present.

Other conditions that share some characteristics with Angelman syndrome include Rett syndrome, Lennox-Gastaut syndrome and non-specific cerebral palsy.

Treatment#

There is no cure for Angelman syndrome, but a child can benefit from a range of treatments for some symptoms, including:

• anti-epileptic medication
• speech therapy and communication therapy
• behaviour modification
• occupational therapy and physical therapy
• special education and social skills training

Angelman syndrome is not a degenerative disease, and children with the condition can expect a normal lifespan.

Support for parents#

Support for parents of children with Angelman syndrome can include respite care, support organisations, genetic counselling and family therapy. Support organisations are often connected with a wide range of groups and can put you in touch with other individuals and families affected by Angelman syndrome.

If a family member has been diagnosed with Angelman syndrome, or the condition runs in your family, it can help to speak to a genetic counsellor. Genetic counsellors are health professionals qualified in both counselling and genetics. As well as providing emotional support, they can help you understand the condition and its causes, how it is inherited, and what a diagnosis means for your child’s health and for your family.

Genetic counsellors are trained to provide information and support that is sensitive to your family circumstances, culture and beliefs. If Angelman syndrome runs in your family, a genetic counsellor can explain the genetic testing options available to you and other family members. You may choose to see a genetic counsellor if you are planning a family, to learn your risk of passing the condition on to a child or to arrange prenatal tests.

Key points#

• Causes of Angelman syndrome include the UBE3A gene being missing, incorrectly inactivated, or changed by a mutation.
• It was once known as “happy puppet syndrome” because of the child’s sunny outlook and jerky movements.
• It is now named after Harry Angelman, the doctor who first investigated the symptoms in 1965.
• Common problems include a very short attention span.
• A lack of UBE3A protein in the brain is thought to be what causes Angelman syndrome.

Where to get help#