Current Research Studies

Angelman Syndrome Natural History Study

Angelman Syndrome Natural History Study


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 help us understand the progression of symptoms associated with AS throughout an individual’s lifetime.  

The Natural History Study is currently recruiting twins, where one or both twins are diagnosed with AS. Researchers will compare data to:
– Find insight into environmental influences on AS
– Determine if genes outside of UBE3A impact individuals and outcome measures
– Compare therapies between twins, in order to better understand their effect


This study is being conducted at:

Find contact information for each site at

Participant Requirements

  • Individuals with Angelman syndrome of any age are welcome. 
  • Be willing to visit a study site at least once for an exam and observations. (There is the virtual visit option if an in-person visit is not feasible for you right now.)

More Information

For more information about the study:  617-919-4800 |

Watch Wen-Hann Tan, MD, research assistants and Amanda Moore and Allyson Berent discuss the Angelman Natural History Study.

Watch Wen-Hann Tan, MD discuss the Angelman Natural History Study at the 2019 ASF Family Conference.



Published Studies

Following is a list of published research using data obtained directly from the Natural History Study. You can see the studies and conclusions by searching on PubMed for the PMID  (PubMed ID).  

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 Sep; 7(9):e837. PMID: 31400086.
  13. Khan N, et al. An observational study of pediatric healthcare burden in Angelman syndrome: results from a real-world study. Orphanet J Rare Dis. 2019 Nov 4; 14(1):239. PMID: 31684986.
  14. Sadhwani A, et al. Neurodevelopmental profile of siblings with Angelman syndrome due to pathogenic UBE3A variants. J Intellect Disabil Res. 2020 Mar; 64(3):246-250. PMID: 31854050.
  15. Gomez DA, et al. Differentiating molecular etiologies of Angelman syndrome through facial phenotyping using deep learning. Am J Med Genet A. 2020 Sep; 182(9):2021-2026. PMID: 32524756.
  16. Frohlich J, et al. High-voltage, diffuse delta rhythms coincide with wakeful consciousness and complexity in Angelman syndrome. Neurosci Conscious. 2020 Jun 14; 2020(1):niaa005. PMID: 32551137.
  17. Keute M, et al. Angelman syndrome genotypes manifest varying degrees of clinical severity and developmental impairment. Mol Psychiatry. 2020 Aug 13. Epub ahead of print. PMID: 32792659.
  18. Sadhwani A, et al. Developmental Skills of Individuals with Angelman Syndrome Assessed Using the Bayley-III. J Autism Dev Disord. 2021 Jan 30. Epub ahead of print. PMID: 33517526.
  19. Ostrowski LM, et al. Delta power robustly predicts cognitive function in Angelman syndrome. Ann Clin Transl Neurol. 2021 May 28. Epub ahead of print. PMID: 34047077.
  20. Veatch OJ, et al. Evaluating Sleep Disturbances in Children with Rare Genetic Neurodevelopmental Syndromes. Pediatr Neurol. 2021 Oct; 123:30-37. PMID: 34388423.
  21. Cassater D, et al. Clinical Characterization of Epilepsy in Children With Angelman Syndrome. Pediatr Neurol. 2021 Nov; 124:42-50. PMID: 34536900.
  22. Hipp JF, et al. Electrophysiological Abnormalities in Angelman Syndrome Correlate With Symptom Severity. Biol Psychiatry Glob Open Sci. 2021 Sep;1(3):201-209. PMID: 34841387.
  23. 23. Grebe SC, et al. Anxiety in Angelman Syndrome. Am J Intellect Dev Disabil. 2022 Jan 1; 127(1):1-10. PMID: 34979033.


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.
  5. Han J, et al. A placebo-controlled trial of folic acid and betaine in identical twins with Angelman syndrome. Orphanet J Rare Dis. 2019 Oct 22; 14(1):232. PMID: 31640736.


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.

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