- 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
- complete intake
- sleeping patterns?
- communications skills?
- developmental assessment?
- services received?
- unusual behaviors? laughter? generally happy?
- problems with balance? walking?
- complete pedigree
- 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
- Short attention span
- normal prenatal and birth history
- Features Present in more than 80% of patients
- caused by delayed head growth
- present by age 2
- Beginning by age 3
- Abnormal EEG
- Characteristic large amplitude slow-spike waves
- Features found in 20-80% of patients
- Hypopigmentation of skin and eyes
- Feeding problems in infancy
- Wide mouth, wide spaced teeth
- Increased sensitivity to heat
- Sleep disturbances
- 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
- 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
- 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
- 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%)
- 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?
- Geneclinics: Angelman syndrome
- Smith's Recognizable Patterns of Human Malformations
- Clinical Genetics Lecture
The information in this outline was last updated in 2002.