Angelman Syndrome

Description of Angelman Syndrome *note: this is a student project that is still being completed

Complex genetic disorder affecting the nervous system. It is characterized by severe learning difficulties, motor dysfunction, seizure disorder, and often a happy, sociable disposition.

Prevalence

Affects approximately 1 in 15,000 individuals (Margolis et al)

Epidemiology

• Onset is usually before the age of 3 (Margolis)
• Caused by 4 molecular mechanisms (Kishino)
  • Maternal deletions of chromosome 15q11-q13 (70-80%)
  • Intragenic mutation in maternally inherited UBE3A which is found in chromosome 15q11-q13 (10-20%)
  • Paternal uniparental disomy (UPD) in chromosome 15q11-q13 (3-5%)
  • Imprinting defects in chromosome 15q11-q13 which change the expression of  UBE3A (3-5%)

• Those with deletion have more severe disease and those with UPD and imprinting have less severe defects (Margolis)

Clinical Presentation

• Observable Presentation
  • Facial features - thin upper lip, wide spaced teeth
  • Scoliosis (20% of children/50% adults)   (reference from guidelines)
• Motor Presentation
  • Motor dysfunction - tremors, jerkiness, ataxia
• Behavioural Presentation
  • Developmental delay is normally seen within the first year of life
    • most patients lack speech completely but those mildly affected can speak a few words
  • Severe intellectual disability
  • Hyperactivity and short attention span
  • Mouthing of objects
  • Happy demeanor with increased laughter, and often an attraction to water
• Additional Comorbidities that present
  • Seizures (60% of individuals)
  • Autism spectrum disorder (ASD),
  • Digestive system complications
    • constipation
    • gastroesophageal reflux

Diagnostic Procedures

Patients with Angelman Syndrome are often diagnosed within their first year of life. Diagnosis should be confirmed with genetic testing to determine DNA methylation (Margolis et al.)

Differential Diagnosis

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Outcome Measures

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Physiotherapy Management and Treatment

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Clinical Guidelines for Angelman Syndrome

For more detailed information on the treatment of Angelman Syndrome across several health care providers, clinical guidelines have been created by the Angelman Syndrome Guideline Development Group. Visit their document here [1].

Additional Resources

Canadian Angelman Syndrome Society:

• Visit their webpage here [2]

FAST: Foundation of Angelman Syndrome Therapeutics

• Visit their webpage here [3]

References

Margolis, Seth S., Gabrielle L. Sell, Mark A. Zbinden, and Lynne M. Bird. "Angelman syndrome." Neurotherapeutics 12, no. 3 (2015): 641-650.

Kishino, Tatsuya, Marc Lalande, and Joseph Wagstaff. "UBE3A/E6-AP mutations cause Angelman syndrome." Nature genetics 15, no. 1 (1997): 70.