John Miles brochure

This is a copy of the page by John Miles, he is no longer able to have the page online, so I am honoured to be able to let this info remain surfable.

Contents List

What is Angelman Syndrome?
Diagnosis
What causes Angelman Syndrome?
Behaviour in Angelman Syndrome?
Clinical features in Angelman Syndrome?
The genetics of Angelman Syndrome?
Is there a treatment for Angelman Syndrome?
Education
Communication in Angelman Syndrome
Epilepsy in Angelman Syndrome
Pigmentation in Angelman Syndrome
The prognosis for adults with Angelman Syndrome
Research into Angelman Syndrome

What is Angelman Syndrome?

Angelman Syndrome (AS) is neurological disorder in which severe learning difficulties are associated with a characteristic facial appearance and behaviour. Dr. Harry Angelman, a paediatrician working in Warrington, Cheshire, first reported three children with this condition in 1965 and it was initially presumed to be rare. In 1987, it was first noted that around half of the children with AS have a small piece of chromosome 15 missing (chromosome 15 deletion). Since this time the condition has been reported more frequently and the incidence is now thought to be 1 in 25,000 children. return to top

Diagnosis of Angelman Syndrome

The diagnosis of AS is usually made by a paediatrician or clinical geneticist and is based on:

• a history of delayed motor milestones and then later a delay in general 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
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  What Causes Angelman Syndrome?

  AS is due to abnormal expression of a group of genes on chromosome 15. It is likely that at least one of these genes controls development of the brain, especially the parts associated with language, movement and pigmentation. It seems also that some genes influence chemical transmission of messages within the brain. All of these hypotheses need further investigation and research, however.
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  Behaviour in Angelman Syndrome

  The behavioural features of AS are very characteristic. They are first apparent as feeding problems in infancy and a poor sleeping pattern. Many AS children require far less sleep than a normal child. The children are typically happy and sociable and laugh with minimum provocation, sometimes inappropriately in situations which others would not find funny. Attention span is short and hyperactivity common. AS children tend to enjoy similar pastimes. They prefer "rough and tumble" games rather than activities which require concentration and they love water. Favourite play things are plastic, balloons, photographs, noisy or musical toys and TV and video. They are sociable, affectionate children who enjoy the company of other people but tend not to interact with them directly. Problem behaviours which have been noted in AS are hair pulling, biting, mouthing and chewing. These problems can be overcome by behaviour modification, although stubbornness is another common Angelman trait! Their natural inquisitiveness can lead them into danger eg: on the roads and in the kitchen. return to top
  
  

  The Clinical Features of Angelman Syndrome

  (Not every patient will show every feature)

• Feeding problems (75%) (poor suck, possetting, 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, 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% return to top
  

  Is there a treatment for Angelman Syndrome?

  There is no cure for AS but there are some treatments for the symptoms of the condition. Epilepsy can be controlled by the use of anticonvulsant medication and physiotherapy is important to encourage joint mobility and prevent stiffening of the joints. Occupational therapy, speech therapy, hydrotherapy and music therapy are also used in the management of this condition.
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  Education

  From the earliest stages, structured play is encouraged for AS children. Thereafter the method of pre-school education most commonly followed is the portage scheme, whereby language, socialization, self-help, cognitive and motor skills are taught in a stepwise fashion. Thereafter, all AS children require specialist education and will need "statementing" for assessment of their educational needs. Placement is usually at a school for children with severe learning disabilities but some children attend mainstream school with specialist help initially, fulfilling the need for integration with normal children. At all schools, AS children participate to the best of their abilities in all subjects of the national curriculum, but in addition there is particular emphasis on the teaching of personal self-help and social skills. A few AS children have undergone the system of conductive education but it is not known at the present time whether this method is of particular benefit to AS children or not. AS is not a progressive condition, and although progress is slow, skills continue to be acquired throughout life.
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  Communication in Angelman Syndrome

  AS children have specific problems with the development of speech. The majority of children have no speech atall or say less than three words, but most will learn to communicate in other ways and speech therapy remains important for the development of communication skills. Around 25% of children are able to use Makaton sign language and others match pictures or symbols to indicate their needs. Some children use only primitive gestures as a means of communication. In almost all cases comprehension is better than expressive speech and the problem with communication remains one of the main areas of concern to parents. Preliminary studies of detailed brain scans suggest that there may be abnormal development of speech areas of the brain but more research is needed in this area.
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  Epilepsy in Angelman Syndrome

  Around 80% of AS children will have a convulsion at some stage in their lives. The commonest time for fits to begin is between 18 and 24 months of age, often associated with a fever. A variety of anticonvulsants have been used to control fits with sodium valproate and clonazepam being some of the more successful. Each child needs treating individually, however, and when fits are difficult to control referral to a paediatric neurologist is important. The fits are often episodic in nature and interspersed with relatively fit-free periods. Common types of seizures include drop attacks, petit mal absences and myoclonic jerks. Infants with AS sometimes present with salaam attacks (infantile spasms). Fits are less frequent as the children grow older and often cease completely. During a severe period of fitting regression in development may occur with the loss of some previously acquired skills. The regression is reversible, however, and the skills are regained at a later date. The EEG tracing is almost always abnormal in AS and has a specific pattern which has been studied in detail. The EEGs need to be carried out under specified conditions to show up all the relevant features and the changes are more prominent in younger children.
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  Pigmentation in Angelman Syndrome Children

  About 60% AS children have less pigment in their skin, hair and eyes than normal and fair hair and blue eyes are commonly seen. The skin is pale and burns easily on exposure to sunlight. The lack of pigment is particularly obvious when looking at the back of the eye and can lead to visual problems such as a squint, roving eye movements (nystagmus) and poor eyesight. The impairment is usually mild and it is unusual for an AS child to have severe visual problems.
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  The prognosis for adults with Angelman Syndrome

  The clinical features of AS 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 recognisable but many Angelman adults look remarkably youthful for their age. Puberty and menstruation begin at around the normal time and although there are no records of an AS individual ever having had a child, sexual development is normal and it is presumed that these adults are fertile. 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 are able to eat with a knife or spoon and fork. Although no-one to date with AS has been capable of living independently, they can learn to perform simple household tasks and are perhaps best suited to life in a community care home where a group of adults are cared for by a supervisor. 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. return to top
  
  

  The Genetics of Angelman Syndrome

  In the majority of families there is only one individual affected by AS. In these families the affected person usually has a piece of one of their chromosome 15s missing (deletion). Deletions can be detected down the microscope or by looking at a person's DNA, their genetic material using special techniques in the laboratory. In cases with a chromosome 15 the parents' chromosomes are usually absolutely normal. Neither parent is a "carrier" AS but the deletion in the child usually arises by chance on the chromosome 15 which came from the mother. If a similar deletion arises on the chromosome 15 which comes from the father, then a completely different condition called Prader-Willi syndrome results. There have been a few families where AS has recurred in a brother or sister and in these cases, there is usually no detectable deletion. In rare cases one parent, usually the mother, does carry a small genetic abnormality on one chromosome which can give rise to AS in a child. Because of this it is important for both parents to have their chromosomes checked. In the vast majority of families the recurrence risk of AS is low, especially if there is a deletion of chromosome 15 and the parents' chromosomes are normal. The genetic situation is complicated, however, and may be different in different families, so referral to a genetic counselling clinic is advised to discuss the genetic situation in each individual family. At present there is no absolutely reliable prenatal diagnostic test available for those families at high risk of recurrence, but advances have been made in this area and there is a good chance that one will be available soon. The majority of families will be at low risk and a prenatal test may not be indicated except for reassurance. Many parents opt to have an amniocentesis test in subsequent pregnancies and again, this is best discussed with a geneticist and/or obstetrician. return to top
  

  Research into Angelman Syndrome

  In recent years there has been some fruitful research into the location and identification of the genes causing AS. Efforts are now been directed towards analysis of the precise function of these genes. There is still much progress to be made, however, in understanding the symptoms of this condition, particularly the communication problems and the seizure disorder. Research therefore falls into two categories:

• Scientific research which involves using laboratory techniques to find out about the basic chemical, physiological and anatomical abnormalities in the condition and aids diagnosis.
• Clinical research which involves the observation and study of patients themselves. Both types of research will be important in the future although it is unlikely that gene therapy will ever be able to cure AS because some of the effects on early brain development are irreversible. Understanding of the genes involved, however, could be a valuable guide as to which of the drugs might be used to treat the condition. Good clinical research can help to teach us more about which therapies are particularly useful in the management of AS. There are now many centres all over the world which are involved in research into AS, Prader-Willi syndrome and "genomic imprinting" (the phenomenon which causes genes to have different effects depending on the parent of origin). With pooling of ideas from all these major centres and help from AS families we should be able to understand more about how the genes on chromosome 15 cause the symptoms of AS. return to top