Current Research Studies

Angelman Syndrome Natural History Study

Angelman Syndrome Natural History Study

Natural History Study Overview

Participation in this study will help better our understanding of how developmentbehavior and communication change in individuals with AS over the course of their lives.

We may know a lot about AS, but there are certain ages and issues that have never been studied. The AS Natural History Study will find out what life with AS is really like throughout the lifetime.  

This study is being conducted at Boston Children’s Hospital and the ASF AS Clinic at Rady Children’s Hospital in San Diego. 

Participant Requirements

  • Individuals with Angelman Syndrome of any age are welcome. 
  • Participants will visit a study location once a year.  At each visit, participants will have a physical exam as well as answer questions and complete surveys. 

More Information

For more information and questions, call (617) 919-6008 or email

Natural History study flyer with pictures of a boy    natural history study flyer

Submitted and Published Studies

Following is a list of submitted and published research using data obtained directly from the Natural History Study. 

Using data / participants from the FDA Natural History Study: 2017 – Present

Submitted / In preparation

Merton CF, Baker EK, et al. [Angelman syndrome adults with independent living skills] – In preparation

Schnur G, Booman A, et al. [Home video pilot project] – Awaiting data collection & analysis


Published by investigators previously or while supported by RDCRN: 2004 – Present

  1. Sahoo T, et al. Microarray based comparative genomic hybridization testing in deletion bearing patients with Angelman syndrome: genotype-phenotype correlations. J Med Genet. 2006 Jun; 43(6):512-6. PMID: 16183798.
  2. Lawson-Yuen A, et al. Atypical cases of Angelman syndrome. Am J Med Genet A. 2006 Nov 1; 140(21):2361-4. PMID: 17036311.
  3. Sahoo T, et al. Identification of novel deletions of 15q11q13 in Angelman syndrome by array-CGH: molecular characterization and genotype-phenotype correlations. Eur J Hum Genet. 2007 Sep; 15(9):943-9. PMID: 17522620.
  4. Peters SU, et al. Double-blind therapeutic trial in Angelman syndrome using betaine and folic acid. Am J Med Genet A. 2010 Aug; 152A(8):1994-2001. PMID: 20635355.
  5. Landsman IS, et al. Are children with Angelman syndrome at high risk for anesthetic complications? Paediatr Anaesth. 2012 Mar; 22(3):263-7. PMID: 21801274.
  6. Tan WH, et al. If not Angelman, what is it? A review of Angelman-like syndromes. Am J Med Genet A. 2014 Apr; 164A(4):975-92. PMID: 24779060.
  7. Bird LM. Angelman syndrome: review of clinical and molecular aspects. Appl Clin Genet. 2014 May 16; 7:93-104. PMID: 24876791.
  8. Margolis SS, et al. Angelman Syndrome. Neurotherapeutics. 2015 Jul; 12(3):641-50. PMID: 26040994.
  9. Tan WH, Bird LM. Pharmacological therapies for Angelman syndrome. Wien Med Wochenschr. 2017 Jun; 167(9-10):205-218. PMID: 26758979.
  10. Tan WH, Bird LM. Angelman syndrome: Current and emerging therapies in 2016. Am J Med Genet C Semin Med Genet. 2016 Dec; 172(4):384-401. PMID: 27860204.
  11. Key AP, et al. Feasibility of using auditory event-related potentials to investigate learning and memory in nonverbal individuals with Angelman syndrome. Brain Cogn. 2018 Dec; 128:73-79. PMID: 30471990.


Using data / participants from the RDCRN Natural History Study: 2006 – 2014

  1. Gentile JK, et al. A neurodevelopmental survey of Angelman syndrome with genotype-phenotype correlations. J Dev Behav Pediatr. 2010 Sep; 31(7):592-601. PMID: 20729760.
  2. Tan WH, et al. Angelman syndrome: Mutations influence features in early childhood. Am J Med Genet A. 2011 Jan; 155A(1):81-90. PMID: 21204213.
  3. Peters SU, et al. Longitudinal follow-up of autism spectrum features and sensory behaviors in Angelman syndrome by deletion class. J Child Psychol Psychiatry. 2012 Feb; 53(2):152-9. PMID: 21831244.
  4. Vendrame M, et al. Analysis of EEG patterns and genotypes in patients with Angelman syndrome. Epilepsy Behav. 2012 Mar; 23(3):261-5. PMID: 22341959.
  5. Miodrag N, Peters S. Parent stress across molecular subtypes of children with Angelman syndrome. J Intellect Disabil Res. 2015 Sep; 59(9):816-26. PMID: 25833412.
  6. Sidorov MS, et al. Delta rhythmicity is a reliable EEG biomarker in Angelman syndrome: a parallel mouse and human analysis. J Neurodev Disord. 2017 May 8; 9:17. PMID: 28503211.
  7. den Bakker H, et al. Abnormal coherence and sleep composition in children with Angelman syndrome: a retrospective EEG study. Mol Autism. 2018 Apr 27; 9:32. PMID: 29719672.
  8. Sadhwani A, et al. Two Angelman families with unusually advanced neurodevelopment carry a start codon variant in the most highly expressed UBE3A isoform. Am J Med Genet A. 2018 Jul; 176(7):1641-1647. PMID: 29737008.
  9. Frohlich J, et al. Electrophysiological Phenotype in Angelman Syndrome Differs Between Genotypes. Biol Psychiatry. 2019 May 1; 85(9):752-759. PMID: 30826071.
  10. Sadhwani A, et al. Maladaptive behaviors in individuals with Angelman syndrome. Am J Med Genet A. 2019 Jun; 179(6):983-992. PMID: 30942555.
  11. Khan N, et al. Healthcare burden among individuals with Angelman syndrome: Findings from the Angelman Syndrome Natural History Study. Mol Genet Genomic Med. 2019 Jul; 7(7):e00734. PMID: 31090212.
  12. Carson RP, et al. Preserved expressive language as a phenotypic determinant of Mosaic Angelman Syndrome. Mol Genet Genomic Med. 2019 Aug 10:e837. PMID: 31400086.


Submitted / In preparation

  1. Sadhwani A, et al. Neurodevelopmental Profile of Siblings with Angelman Syndrome due to pathogenic UBE3A variants. J Intellect Disabil Res. – Revision submitted
  2. Khan N, et al. An Observational Study of Pediatric Healthcare Burden in Angelman Syndrome: Results from a Real-World Study. Orphanet J Rare Dis. – Revision in preparation
  3. Frohlich J, et al. Emergence of consciousness and complexity amidst diffuse delta rhythms: the paradox of Angelman syndrome – Submitted
  4. Keute M, et al. Clinical severity and developmental impairment in Angelman syndrome differ with genotype. – In preparation
  5. Sadhwani A, Wheeler AC, et al. A longitudinal investigation of developmental performance on the Bayley-III in individuals with Angelman Syndrome: Findings from the Angelman Syndrome Natural History Study. – In preparation
  6. Sadhwani A, Wheeler AC, et al. [Vineland longitudinal analysis] – In preparation
  7. Sadhwani A, et al. [Developmental milestones] – In preparation
  8. Booman A, Merton CF, et al. [Longitudinal analysis of parental stress and family QOL] – Data analysis


Other studies supported directly by the RDCRN infrastructure: 2006 – 2014

  1. Peters SU, et al. Alterations in white matter pathways in Angelman syndrome. Dev Med Child Neurol. 2011 Apr; 53(4):361-7. PMID: 21121904.
  2. Bird LM, et al. A therapeutic trial of pro-methylation dietary supplements in Angelman syndrome. Am J Med Genet A. 2011 Dec; 155A(12):2956-63. PMID: 22002941.
  3. Goldman SE, et al. Sleep in children and adolescents with Angelman syndrome: association with parent sleep and stress. J Intellect Disabil Res. 2012 Jun; 56(6):600-8. PMID: 22044653.
  4. Tan WH, et al. A randomized controlled trial of levodopa in patients with Angelman syndrome. Am J Med Genet A. 2018 May; 176(5):1099-1107. PMID: 28944563.

The Angelman Syndrome Foundation does not endorse any clinical trial or study, but provides information to the AS community for its own consideration.