Handbook of Genetic Counseling/Angelman Syndrome-2

From Wikibooks, open books for an open world
< Handbook of Genetic Counseling
Jump to: navigation, search

Angelman Syndrome

Introduction[edit]

  • Introduce myself
  • What are the major concerns that you would like to have addressed today?
  • Who referred you to genetics?
  • Outline session
    • obtain medical history and family history
    • Dr. Saal will come in and do physical exam
    • discuss condition and testing options
    • address specific concerns

Medical History[edit]

  • complete intake
    • seizures?
    • medications?
    • sleeping patterns?
    • communications skills?
    • hyperactivity?
    • developmental assessment?
    • services received?
    • unusual behaviors? laughter? generally happy?
    • problems with balance? walking?
    • MRI?
  • complete pedigree

Incidence[edit]

  • 1/12,000-1/20,000

Clinical Features[edit]

  • Feature present in about 100% of patients
    • normal prenatal and birth history
      • normal birth weight and head circumference
      • no major birth defects
    • normal metabolic and hematologic profile
    • structurally normal brain on MRI
      • mild cortical atrophy or dysmyelination possible
    • delayed motor development
      • apparent by 6-12months
      • usually severe
    • speech impairment
      • usually < 1 or 2 words
      • receptive language better than expressive language
    • movement and balance disorder
      • abnormal gait
      • tremulous movements of limbs
    • Unusual behaviors
      • Frequent laughter and smiling/happy demeanor
      • Excitability
      • Hyperactivity
      • Short attention span
  • Features Present in more than 80% of patients
  • Microcephaly
    • caused by delayed head growth
    • present by age 2
  • Seizures
    • Beginning by age 3
  • Abnormal EEG
    • Characteristic large amplitude slow-spike waves
  • Features found in 20-80% of patients
    • Strabismus
    • Hypopigmentation of skin and eyes
    • Feeding problems in infancy
    • Wide mouth, wide spaced teeth
    • Increased sensitivity to heat
    • Sleep disturbances

Management[edit]

  • Behavioral modification for undesirable/socially unacceptable behaviors
  • Medication for seizures
  • Generally do not receive medication for hyperactivity
  • Occupation therapy for fine motor control
  • Speech therapy focusing on nonverbal means of communication
  • Safe, confining bedroom for nighttime sleeplessness
  • Monitoring for onset of scoliosis

Genetics[edit]

  • Caused by loss of maternal contribution of region 15q11-q13
    • 65-75% of patients have 3-5Mb interstitial deletion
    • 3-7% of patients have paternal uniparental disomy
    • 2-6% of patients have imprinting defect
    • 5-11% of patients have mutations in the UBE3A gene within this region
    • 11-20% of patients have another unknown cause

Molecular Testing[edit]

  • DNA methylation analysis
    • 78% of patients with a deletion, uniparental disomy, or an imprinting defect are detected this way
    • further testing is required to distinguish between these types
      • FISH analysis can detect deletions (70% of patients)
      • DNA polymorphism testing can detect uniparental disomy
      • Patients with imprinting defects have 15q11-q13 polymorphisms from both parents
        • imprinting center defect characterization available on research basis only
  • UBE3A mutation analysis
    • 11% of patients with Angelman syndrome have identifiable mutations

Recurrence Risks[edit]

  • Families Genetic Mechanism Risk to Siblings
    • 65-75% 3-5Mb deletion <1%
    • <1% unbalanced translocation as high as 50%
  • small interstitial deletion
    • 3-7% paternal uniparental disomy <1%
    • <1% uniparental disomy with approaching 100% Robertsonian translocation
    • 1-3% imprinting defect as high as 50% (if deletion in imprinting center mother has deletion)
    • 1-3% imprinting defect likely <1% without deletion
    • 11% UBE3A mutation as high as 50% if mother has deletion
    • 10-15% other unidentifiable cause most cases not familial (but could be as high as 50%)

Psychosocial Issues[edit]

  • Who is involved in care of patient?
  • What is the living situation?
  • How will having a diagnosis change care and management?
  • How will having a diagnosis affect you?
  • Are there concerns about recurrence risks?

References[edit]

  • Geneclinics: Angelman syndrome
  • Smith's Recognizable Patterns of Human Malformations
  • Clinical Genetics Lecture

Notes[edit]

The information in this outline was last updated in 2002.