Angelman Syndrome Craig Dobson, MD CPT, MC, USAR NCC Pediatrics 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. Angelman Features Seizures Developmental delay/MR DQ20-35 Strabismus Sleep disturbance Hypermotoric behavior/tremulousness Ataxia Excessive happiness Constipation Microcephaly Multiple Genetic Mechanisms Overall cause is loss of maternally imprinted copy of genes on Chr15. Prader-Willi is parental lost. 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%) 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. 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 Management, cont. Sleep disturbance – Create “safe sleeping” area • High rails • Cushioning • Low to floor – Medications: • Chloral • Benedryl • Melatonin 0.3mg 1hr prior to sleep 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 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 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.