Angelman syndrome (AS) and is typically diagnosed in children under the age of three based upon early behavioural concerns identified by parents, or genetic links with other family members. For some families however, the pathway to diagnosis is not so clear, particularly when children demonstrate differential characteristics, commonly seen for those with UBE3A pathogenic variants (ubiquitin protein ligase EA3), imprinting defects or uniparental disomy (patUPD) etiology. The aim of this paper is to explore parent’s experiences of the pathway to diagnosis involving 394 children with formal diagnoses of AS.
Data from the Global Angelman Syndrome Registry on the age of formal diagnosis, the process involved in formal diagnosis, professionals involved in the diagnosis, the number of tests taken and the prevalence of misdiagnoses were compared across deletion and non-deletion (UBE3A pathogenic variant, imprinting and patUPD) etiologies.
Compared to those with deletion etiology, individuals with non-deletions are more likely to (a) receive a diagnosis later in childhood (i.e., past the age of 3 years old), (b) have a greater number of professionals and tests involved and (c) to be misdiagnosed with global developmental delay.
The methods identified for formal diagnoses mirrored the current advances in technology and accessibility. The benefit of using parental report from registries to understand the diagnostic process and promote early and accurate diagnosis of AS is discussed.
This data is available on request to the data management committee. Please email email@example.com for requests.
Bailus, B. J., & Segal, D. J. (2014). The prospect of molecular therapy for Angelman syndrome and other monogenic neurologic disorders. BMC Neuroscience, 15, 76.
Keute, M., Miller, M. T., Krishnan, M. L., Sadhwani, A., Chamberlain, S., Thibert, R. L., Tan, W. H., Bird, L. M., & Hipp, J. F. (2020). Angelman syndrome genotypes manifest varying degrees of clinical severity and developmental impairment. Molecular Psychiatry, 1–9.
Lossie, A. C., Whitney, M. M., Amidon, D., Dong, H. J., Chen, P., Theriaque, D., Hutson, A., Nicholls, R. D., Zori, R. T., Williams, C. A., & Driscoll, D. J. (2001). Distinct phenotypes distinguish the molecular classes of Angelman syndrome. Journal of Medical Genetics, 38, 834–845.
Maranga, C., Fernandes, T. G., Bekman, E., & da Rocha, S. T. (2020). Angelman syndrome: A journey through the brain. The FEBS Journal, 2154-2175.
Raspa, M., Levis, D. M., Kish-Doto, J., Wallace, I., Rice, C., Barger, B., Green, K. K., & Wolf, R. B. (2015). Examining parents’ experiences and information needs regarding early identification of developmental delays: Qualitative research to inform a public health campaign. Journal of Developmental and Behavioral Pediatrics, 36, 575.
Roche, L., Sigafoos, J., & Trembath, D. (2020). Augmentative and alternative communication intervention for people with Angelman Syndrome: A systematic review. Current Developmental Disorders Reports, 7, 28–34.
Sadhwani, A., Willen, J. M., LaVallee, N., Stepanians, M., Miller, H., Peters, S. U., Barbieri-Welge, R. L., Horowitz, L. T., Noll, L. M., Hundley, R. J., Bird, L. M., & Tan, W. H. (2019). Maladaptive behaviors in individuals with Angelman syndrome. American Journal of Medical Genetics Part A, 179, 983–992.
Taylor, S., Wright, A. C., Pothier, H., Hill, C., & Rosenberg, M. (2019). It’s like i have an advantage in all this: experiences of advocacy by parents of children with disabilities from professional backgrounds. Journal of Society & Social Welfare, 46, 159–184.
Warr, D., Dickinson, H., Olney, S., Hargrave, J., Karanikolas, A., Kasidiset, V., Katsikis, G., Ozge, J., Peters, D., Wheeler, J., & Wilcox, M. (2017). Choice, control and the NDIS. Melbourne: Melbourne Equity Institute.
Watson, S. L. (2008). “Something you have to do”-Why do parents of children with developmental disabilities seek a differential diagnosis? Developmental Disabilities Bulletin, 36, 168–198.
Williams, C. A., Beaudet, A. L., Clayton-Smith, J., Knoll, J. H., Kyllerman, M., Laan, L. A., Magenis, R. E., Moncla, A., Schinzel, A. A., Summers, J. A., & Wagstaff, J. (2006). Angelman syndrome 2005: Updated consensus for diagnostic criteria. American Journal of Medical Genetics Part A, 140, 413–418.
Zhang, D., Kaufmann, W. E., Sigafoos, J., Bartl-Pokorny, K. D., Krieber, M., Marschik, P. B., & Einspieler, C. (2017). Parents’ initial concerns about the development of their children later diagnosed with fragile X syndrome. Journal of Intellectual & Developmental Disability, 42, 114–122.
We would like to thank the parents and children for the time they took to complete the registry.
Centre for Children’s Health Research, The University of Queensland, Brisbane, Australia
Laura Roche, Megan Tones & Helen Heussler
School of Education, University of Newcastle, University Drive, Callaghan, NSW, 2308, Australia
Queensland University of Technology, Brisbane, Australia
Developmental Disorders Group, Mater Research Institute, The University of Queensland, Brisbane, Australia
Mark G. Williams
Foundation for Angelman Syndrome Therapeutics (FAST), Salisbury, Australia
Meagan Cross & Chloe Simons
Children’s Health Queensland, Brisbane, Australia
LR: developed the concept and design for the study, assisted with the analysis of results, and wrote the manuscript. MT: assisted in the concept and design of the study, analysed the data, collaborated in writing the manuscript, and is the curator of the Global Angelman Syndrome Registry. MGW: provided expert sections on the genetic mechanisms of diagnosing Angelman syndrome and collaborated in the editing of the manuscript. MC and CS: assisted in the design of the original cohort, collaborated in the writing and editing of the manuscript. HS: assisted in the design of the original cohort, collaborated in the concept and design of the study and collaborated in the data analysis and editing of the manuscript.
Correspondence to Laura Roche.
Ethics was approved by Mater Misericordiae Ltd Human Research Ethics Committee (approval number EC00332).
All participants provided informed consent via an electronic consent process. Participants were unable to view or complete registry modules without completion of the consent process.
Conflict of interest
The authors declare that they have no conflict of interest.