Angelman Syndrome Details

Expanded Description

WHAT IS ANGELMAN SYNDROME (AS)
AS is a rare, non-degenerative, genetic condition first identified in 1965 by Dr Harry Angelman (from whom it gained its name). In simple terms, it is caused by various irregularities in Chromosome 15. These are known as: Deletion positive (del+), UBE3A mutation, Uniparental disomy (UPD), Imprinting defect, and Clinical/other.

Infants often have feeding problems, reflux, and need less sleep than usual. Delayed development becomes noticeable by the age of 6 to 12 months. General characteristics include global developmental delays, severe speech impairment, hyperactivity, a short attention span, jerky movements and balance issues (ataxia), and a fascination with water. Other symptoms, such as recurrent seizures (epilepsy) can appear in early childhood.

AS is often misdiagnosed as Autism or Cerebral Palsy. To ensure the best care and treatment, seek a genetic diagnosis. Early and continued participation in therapies such as Physiotherapy (PT); Occupational Therapy (OT); Speech Language Therapy (SLT); Treatment for feeding/reflux (Gastroenterology); and Treatment for epilepsy (Neurology), can significantly improve the prognosis.

People with AS are affectionately known as ‘angels’ due to their typical happy demeanour, frequent smiles and laughter, and affectionate nature. General health is usually fairly good, and life-span is near average. There is a very active and supportive international Angelman community.

Prevalence

6.5 ( Per 100,000 Population ) [Source]

Causes

What Causes Angelman Syndrome?

Angelman Syndrome is caused by a severe reduction of expression of the gene UBE3a in the brain. UBE3A is a ubiquitin ligase whose function and targets relevant to AS are still unknown.

15q11.2-q13 deletions (~68% of cases) – the majority of AS cases are caused by deletions on the maternal copy of Chromosome 15. Due to genomic imprinting, only the maternal copy of UBE3A is expressed in the brain. The deletion thus removes the normal expression of this gene in AS individuals.

UBE3A mutations (~11% of cases) – In these individuals, mutations in the UBE3A gene either prevent its expression or function. Thus these individuals do not have the appropriate levels of fuctional UBE3A in the brain.

Uniparental disomy (UPD; ~7% of cases) – in UPD, the individual has two copies of paternal Chromosome 15. Because UBE3A is not expressed from the paternal copy, these individuals lack normal levels of UBE3A in the brain.

Imprinting defect (~3% of cases) – These individuals may have a deletion of the imprinting center an Chromosome 15, but cases can also be caused by loss of imprinting information during the mother’s oogenesis. Loss of imprinting will prevent expression of the maternal UBE3A gene in the brain.

Clinical/other (~11%) – In these individuals, all testing for Angelman Syndrome is normal, but they still meet the diagnostic criteria for AS. These individuals may have as yet unrecognized mutations that affect UBE3A or genomic imprinting on Chromosome 15. Please note that there are several other syndromes that present like AS that can be tested for.

Summarized from GeneReviews on Angelman Syndrome by C.A. Williams and D.J. Discoll

Disorder Symptoms

Diagnostic Criteria for Angelman Syndrome
• Behavioural uniqueness: any combination of frequent laughter/smiling; apparent happy demeanor; easily excitable personality, often with hand flapping movements; hypermotoric behaviour; short attention span (100%)
• Speech impairment, none or minimal use of words; receptive and nonverbal communication skills higher than verbal ones (100%)
• Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs (100%)
• Developmental delay, functionally severe (100%)
• Seizures, onset usually <3 years of age (80%)
• Feeding problems during infancy (20-80%)
• Uplifted, flexed arm position especially during ambulation (20-80%)
• Sleep disturbance (20-80%)
• Attraction to/fascination with water (20-80%)
• Increased sensitivity to heat (20-80%)
• Abnormal EEG, characteristic pattern with large amplitude slow-spike waves (usually 2-3/s), facilitated by eye closure (80%)
• Hypo-pigmented skin, light hair and eye colour (compared to family), seen only in deletion cases (20-80%)
• Wide mouth, wide-spaced teeth (20-80%)
• Frequent drooling (20-80%)
• Excessive chewing/mouthing behaviour (20-80%)
• Tongue thrusting; suck/swallowing disorders (20-80%)
• Protruding tongue (20-80%)
• Delayed, disproportionate growth in head circumference, usually resulting in microcephaly (absolute or relative) by age 2 (80%)
• Flat occiput (20-80%)
• Occipital groove (20-80%)
• Strabismus (20-80%) an eye condition
• Hyperactive lower limb deep tendon reflexes (20-80%)
From: “Angelman syndrome 2005: updated consensus for diagnostic criteria.” Williams CA et al, Am J Med Genet A. 2006 Mar 1; 140(5):413-8. PMID: 16470747

We don't have any symptoms yet.

Diagnosis

After considering the Diagnostic Criteria for Angelman Syndrome (listed above) and seeking genetic testing, the following variations of irregularities in Chromosone 15, may be diagnosed:

1. Deletion positive (del+) the majority of AS cases are caused by deletions on the maternal copy of Chromosome 15. Due to genomic imprinting, only the maternal copy of UBE3A is expressed in the brain. The deletion thus removes the normal expression of this gene in AS individuals.

2. UBE3A mutations (~11% of cases) – In these individuals, mutations in the UBE3A gene either prevent its expression or function. Thus these individuals do not have the appropriate levels of fuctional UBE3A in the brain.

3. Uniparental disomy (UPD; ~7% of cases) – in UPD, the individual has two copies of paternal Chromosome 15. Because UBE3A is not expressed from the paternal copy, these individuals lack normal levels of UBE3A in the brain.

4. Imprinting defect (~3% of cases) – These individuals may have a deletion of the imprinting center an Chromosome 15, but cases can also be caused by loss of imprinting information during the mother’s oogenesis. Loss of imprinting will prevent expression of the maternal UBE3A gene in the brain.

5. Clinical/other (~11%) – In these individuals, all testing for Angelman Syndrome is normal, but they still meet the diagnostic criteria for AS. These individuals may have as yet unrecognized mutations that affect UBE3A or genomic imprinting on Chromosome 15. Please note that there are several other syndromes that present like AS that can be tested for.

Summarized from GeneReviews on Angelman Syndrome by C.A. Williams and D.J. Discoll

AS is a rare, non-degenerative, genetic condition; general health is usually fairly good, and life-span is near average.

Diagnostic Tests

No diagnostic test information has been added yet.

We don't have any tests yet.

Disorder Treatments

AS is often misdiagnosed as Autism or Cerebral Palsy. To ensure the best care and treatment, seek a genetic diagnosis.

Early and continued participation in therapies such as:

Physiotherapy (PT)
Occupational Therapy (OT)
Speech Language Therapy (SLT)
Treatment for feeding/reflux (Gastroenterology)
Treatment for epilepsy (Neurology)

can significantly improve the prognosis.

We don't have any treatments yet.

Prognosis

AS adults will need to be looked after their whole life. There are many different solutions to this, and it can be approached from many different perspectives depending on the family situation, involvement, finances and cultural values.

Tips for Living with the Disorder

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