Angelman Syndrome

Craig Dobson, MDCPT, MC, USARNCC 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

SeizuresDevelopmental delay/MR DQ20-35StrabismusSleep disturbanceHypermotoric behavior/tremulousnessAtaxiaExcessive happinessConstipationMicrocephaly

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.