Scoliosis and other Disabilities


Angelman syndrome

Is caused by the loss of the normal maternal contribution to a region of chromosome 15, most commonly by deletion of a segment of that chromosome. Other causes include uniparental disomy, translocation, or single gene mutation in that region.

A healthy person receives two copies of chromosome 15, one from mother, the other from father. However, in the chromosome’s region critical for Angelman syndrome, the maternal and paternal contribution express certain genes differently.

This is because of sex-related epigenetic imprinting; the biochemical mechanism is DNA methylation. If they lose the maternal contribution, the result is Angelman syndrome. (When the paternal contribution is lost, by similar mechanisms, the result is Prader-Willi syndrome.)

Angelman syndrome can also result from mutation of a single gene. This gene (Ube3a, part of the ubiquitin pathway) is present on both the maternal and paternal chromosomes, but differs in the pattern of methylation (Imprinting).

The paternal silencing of the Ube3a gene occurs in a brain region-specific manner; the maternal allele is active almost only in the hippocampus and cerebellum.

The most common genetic defect leading to Angelman syndrome is an ~4Mb (mega base) maternal deletion in chromosomal region 15q11-13 causing an absence of Ube3a expression in the maternally imprinted brain regions.

Ube3a codes for an E6-AP ubiquitin ligase, which chooses its substrates selectively, and the four identified E6-AP substrates have shed little light on the possible molecular mechanisms underlying the human Angelman syndrome mental retardation state.

Initial studies of mice that do not express maternal Ube3a show severe impairments in hippocampal memory formation. Most notably, there is a deficit in a learning paradigm that involves hippocampus-dependent contextual fear conditioning.

In addition, it disrupts maintenance of long-term synaptic plasticity in hippocampal area in Ube3a -/- mice. These results provide links amongst hippocampal synaptic plasticity in vitro, formation of hippocampus-dependent memory in vitro, and the molecular pathology of Angelman syndrome.


  • Feeding problems (75%) (poor suck, poor weight gain)
  • Delay in sitting and walking
  • Absent speech
  • Poor attention span and hyperactivity
  • Severe learning disabilities
  • Epilepsy (80%) and an abnormal EEG
  • Unusual movements (fine tremors, hand flapping, jerky movements)
  • Affectionate nature and frequent laughter
  • Wide-based stiff-legged gait
  • Below average head size, often with flattening at the back
  • Subtle, but characteristic facial features (wide, smiling mouth, prominent chin, thin upper lip, deep-set eyes, a tendency to hold tongue between the lips)
  • Fair hair and blue eyes (60%)
  • Poor sleeping pattern
  • Squint (40%)
  • Scoliosis (curvature of the spine) in 10%


It base the diagnosis of Angelman syndrome on:

A history of delayed motor milestones and then later a delay development, especially of speech unusual movements including fine tremors, jerky limb movements, hand flapping and a wide-based, stiff-legged gait.

  • Characteristic facial appearance.
  • A history of epilepsy and an abnormal EEG tracing.
  • A happy disposition with frequent laughter
  • A deletion on chromosome 15


There is no cure for AS but there are treatments for the symptoms of the condition. The use of anticonvulsant medication can control epilepsy and physiotherapy is important to encourage joint mobility and prevent stiffening of the joints.

We also use occupational therapy, speech therapy, hydrotherapy and music therapy in the management of this condition.


The clinical features of Angelman syndrome alter with age. As adulthood approaches, hyperactivity and poor sleep patterns improve. The fits decrease in frequency and often cease altogether and the EEG abnormalities are less obvious.

The facial features remain recognizable but many Angelman adults look remarkably youthful for their age. Puberty and menstruation begin at around the normal time. Sexual development is thought to be normal as evidenced by a single case report of a woman with Angelman syndrome conceiving a female child who also had Angelman syndrome.

The majority of those with AS achieve continence by day and some by night. Dressing skills are variable and usually limited to items of clothing without buttons or zips. Most adults can eat with a knife or spoon and fork.

They can learn to perform simple household tasks. General health is fairly good and life-span near normal. Particular problems which have arisen in adults are a tendency to obesity (more in females) and worsening of scoliosis if it is present.

The affectionate nature which is also a positive aspect in the younger children may also persist into adult life where it can pose a problem socially, but this problem is not insurmountable.

This div height required for enabling the sticky sidebar