1. Angelman Syndrome Craig Dobson, MD CPT, MC, USAR NCC Pediatrics

2. Case 20mo male with h/o developmental delay, presents for evaluation of constipation. PMH: –Frequent seizures, multiple anticonvulsants. –Chromosome analysis normal. –Surgeries: strabismus correction planned. Physical exam –Notable for a happy, giggling child, also slight jitteriness with movements.

3. Angelman Features Seizures Developmental delay/MR DQ20-35 Strabismus Sleep disturbance Hypermotoric behavior/tremulousness Ataxia Excessive happiness Constipation Microcephaly

4. Multiple Genetic Mechanisms Overall cause is loss of maternally imprinted copy of genes on Chr15. Prader-Willi is parental lost.

5. Causes of lost maternal imprint Deletion on maternal chromosome 15. (70%) Uniparenteral disomy of Chromosome 15 (2-3%) –Two copies of father’s Chr 15. Mutation of maternal UBE3A gene. (5-7%) Imprinting defect (3-5%) Unknown (15%)

6. Angelman Sx Sz. Management Seizure Management –Partial motor, often minor movements –Difficult to distinguish from tremulousness. –Often difficult to control. –Valproate and clonazepam often work best.

7. Management, cont Developmental delay –Minimum of spoken words, ~20 –Begin non-verbal communication early. Sign, difficult with ataxia Picture boards Ataxia –Supportive sitting –Gait training

8. Management, cont. Sleep disturbance –Create “safe sleeping” area High rails Cushioning Low to floor –Medications: Chloral Benedryl Melatonin 0.3mg 1hr prior to sleep

9. Management, cont. Orthopedic problems –90% of AS children learn to walk. –However, commonly have subluxed or pronated ankles or tight gastrocs. –May require bracing and alignment surgeries. –Scoliosis is common

10. Prognosis/Outcome Adulthood –Improvement of hyperactivity/Sleep patterns. –Daytime continence usually achieved. –Reduced seizure activity. –May transition to group home, but not independent. –Worsening scoliosis

11. Prognosis/Outcomes Adulthood, cont. –Improve in receptive speech and sign language. –Limited expressive speech (~20 words). –Most walk, but may need assistive devices. –Normal life span.