Overview: Angelman syndrome is a neuro-genetic disorder, caused by genomic imprinting. The deletion or inactivation of genes on the maternally inherited chromosome 15 while the paternal copy, which may be of normal sequence, is imprinted and therefore silenced causes the condition. It is the sister syndrome of Prader-Willi syndrome.
Phenotype/Characteristics: A patient with Angelman syndrome will have the following signs and symptoms:
- a severe delay in development from 6-12 months
- speech problems (most children do not speak or only say a few words)
- movement or balance problems – usually ataxia (loss of co-ordination) and jerky movements of the limbs
A child with Angelman syndrome will also display distinctive behaviours, these may include:
- frequent laughter and smiling, with little stimulus
- being easily excitable, often flapping the hands
- being restless
- having a short attention span
Many children with Angelman syndrome will have microcephaly by the age of two, and many will develop seizures around this age.
Some children with Angelman syndrome will also have the following features and behaviours:
- a flattened skull at the back
- a tendency to stick out the tongue
- feeding problems during infancy
- a prominent chin
- a wide mouth and wide-spaced teeth
- frequent drooling
- excessive chewing
- pale skin and light hair and eye colour
- uplifted bent arms, especially during walking
- increased sensitivity to heat
- disturbed sleep, and needing less sleep than usual
- attraction to, or fascination with, water
Frequency: Angelman syndrome affects an estimated 1 in 12,000 to 20,000 people.
Diagnosis: A deletion or inactivity on chromosome 15 by array comparative genomic hybridization (aCGH) or by BACs-on-Beads technology can be a diagnostic method. FISH-metaphase or interphase, sequence analysis of the coding region and the like may also be used. Prenatal diagnosis is also feasible.
Causes: The condition is caused by the malfunction of the UBE3A gene on chromosome number 15. Normally, both parental copies of the gene are active in the body’s tissues. In certain areas of the brain, only the gene inherited from the mother is active. If the maternal copy of the UBE3A gene is lost because of a chromosomal change or a gene mutation, a person will have no active copies of the gene in some parts of the brain.
In most cases of Angelman syndrome, the child's maternal copy of the UBE3A gene is not functioning normally or is missing altogether.
Several different genetic mechanisms can inactivate or delete the maternal copy of the UBE3A gene. Most cases of Angelman syndrome (about 70 percent) occur when a segment of the maternal chromosome 15 containing this gene is deleted. In other cases (about 11 percent), Angelman syndrome is caused by a mutation in the maternal copy of the UBE3A gene.
In a small percentage of cases, Angelman syndrome results when a person inherits two copies of chromosome 15 from his or her father (paternal copies) instead of one copy from each parent (paternal uniparental disomy). Rarely, Angelman syndrome can also be caused by a chromosomal rearrangement called a translocation, or by a mutation or other defect in the region of DNA that controls activation of the UBE3A gene. These genetic changes can abnormally turn off (inactivate) UBE3A or other genes on the maternal copy of chromosome 15.
Treatment/Recommendations/Therapies: There is no cure for Angelman syndrome and some of the symptoms can be difficult to manage.
The following treatments and aids may augment the effects of the condition to a certain extent:
- Anti-epileptic medicine to control the seizures –sodium valproate, clonazepam and ethosuccimide are some of the drugs in common use.
- Physiotherapy, attention to their sitting posture, a back brace and possibly spinal surgery to prevent their spine from curving further (preventing scoliosis).
- A feeding tube and other feeding aids, especially in infancy. In older children, weight gain may be a problem.
- Occupational therapy to help them develop skills needed for dressing, feeding and other daily living activities.
- An ankle foot orthosis (lower leg brace) to help them walk independently.
- Picture boards, eye gaze technology and other visual aids to help them communicate.
Therapeutic horseriding, swimming, hydrotherapy and music therapy have been reported to be beneficial.
Additional Fact: In the 2011 Philippine drama series Budoy, the titular character and main protagonist Budoy Maniego (played by Filipino actor Gerald Anderson) is diagnosed with Angelman Syndrome.
Angelman syndrome foundation
NHS. (2012). Angelman syndrome. NHS. Retrieved March 12, 2013 from the URL: http://www.nhs.uk/conditions/angelman-syndrome/Pages/Introduction.aspx
Genetics Home reference (2012). Angelman Syndrome. Retrieved March 12, 2013 from the URL: http://ghr.nlm.nih.gov/condition/angelman-syndrome