Table 5.

Treatment of Manifestations in Individuals with Angelman Syndrome

Manifestation/
Concern		TreatmentConsiderations/Other
Seizures Standardized treatment w/ASM by experienced neurologist:
  • Single medication use is preferred, but seizure breakthrough is common.
  • Some w/uncontrollable seizures have benefited from a ketogenic or low-glycemic diet. 1
  • Many ASMs may be effective; none has been demonstrated effective specifically for this disorder. 2
  • Treat NCSE. 3
  • Treat NEM. 4
  • Provide rescue medication.
  • Educate parents/caregivers. 5
Hypermotoric
behaviors
  • Accommodation by the family & provision of a safe environment
  • Children w/AS w/excessive hypermotoric behaviors need an accommodating classroom space
  • Most children do not receive drug therapy for hyperactivity, but some may benefit from use of stimulant medications (e.g., Ritalin®).
  • Typically resistant to behavior therapies
Sleep
disturbance 		Safe but confining bedrooms to accommodate disruptive nighttime wakefulnessAdministration of 0.3 mg melatonin 1 hr before sleep may be helpful, but should not be given in the middle of the night if the child awakens.
Socially disruptive or
self-injurious
behaviors 		Behavior modification can be effective.
Motor delay
  • OT may help improve fine-motor & oral-motor control.
  • Unstable or nonambulatory children may benefit from PT.
  • Special adaptive chairs or positioners may be required, esp for extremely ataxic children.
Special physical provisions in the classroom, along w/teacher aides or assistants, may be needed for effective class integration.
Speech delay
  • Speech therapy is essential & should focus on nonverbal methods of communication.
  • Use of augmentative communication aids (e.g., picture cards, communication boards) at the earliest appropriate time
  • Attempts to teach signing should begin as soon as child is sufficiently attentive.
Individualization & flexibility in the school are important educational strategies.
Gastroesophageal
reflux 		Standard treatments per gastroenterologist:
  • Upright positioning
  • Motility drugs
Sometimes fundoplication is required.
Poor weight gain /
Failure to thrive 		Newborns may require feeding therapy, special nipples, & other strategies to manage weak or uncoordinated sucking.
Constipation Often requires use of high fiber or lubricating agents
Abnormal vision
&/or strabismus 		Standard treatment(s) as recommended by ophthalmologistCommunity vision services through early intervention or school district
Scoliosis
  • Thoraco-lumbar jackets as needed
  • Those w/severe curvature may benefit from surgical rod stabilization
Older adults tend to become less mobile & less active; attention to activity schedules may be helpful in reducing scoliosis & obesity.
Other orthopedic
manifestations 		Subluxed or pronated ankles or tight Achilles tendons can be corrected by orthotic bracing or surgery

ASM = anti-seizure medication; NCSE = nonconvulsive status epilepticus; NEM = nonepileptic myoclonus; OT = occupational therapy; PT = physical therapy

1.
2.

Anticonvulsants most commonly used in the initial approach to treatment include clobazam, levetiracetam, lamotrigine, and clonazepam, based on clinical survey use [Shaaya et al 2016, Prasad et al 2018]. Other anti-seizure medication, less frequently used, have minimal data regarding efficacy (e.g., brivaracetam, cenobamate, felbamate, gabapentin, lacosamide, pregabalin, rufinamide, tiagabine, or cannabidiol). A parent survey suggested relatively diminished benefit from phenobarbital, primidone, carbamazepine, phenytoin, valproic acid, and vigabatrin [Nolt et al 2003]. A few individuals with AS have infrequent seizures and do not require anti-seizure medication.

3.

Diazepam can be useful in outpatient treatment of NCSE [Worden et al 2018].

4.

NEM can be difficult to treat; levetiracetam, clobazam, and clonazepam have been used [Pollack et al 2018]. There is a recent report of success with perampanel [Kawano et al 2020].

5.

Individuals with AS and seizure history should have availability of rescue medications for emergency treatment of prolonged seizures, including rectal diazepam gel or intranasal midazolam or diazepam [Fedak Romanowski et al 2021]. Education of parents/caregivers regarding common seizure presentations is appropriate. For information on non-medical interventions and coping strategies for children diagnosed with epilepsy, see Epilepsy Foundation Toolbox.

From: Angelman Syndrome

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.