OBJECTIVES: Angelman syndrome (AS) is a rare genetic disorder caused by loss of UBE3A expression in neurons and characterized by generalized developmental delay, including severe intellectual disability. Treatment options are limited and focus on symptom management. It is unknown how many people are affected by AS. We aimed to determine the global prevalence of AS to help describe the full burden of this condition.

METHODS: This systematic literature review (SLR) identified English-language population-based studies indexed in MEDLINE and EMBASE through March 2023 or presented at relevant congresses (2021-2023) reporting on AS prevalence. Screening and data extraction were conducted by 1 researcher; a second researcher conducted quality checks. If not specified in studies, prevalence was approximated using the reported number of cases and the population size of the relevant geography during the reporting period.

RESULTS: Of 203 unique publications identified, 10 independent studies met eligibility criteria. Studies (mostly of retrospective design) were conducted in Europe (5 studies), Asia (3), North America (1), and Australia (1) and were heterogenous in terms of sample size, availability of genetic confirmation, time period, and reference population. The estimated AS prevalence per 10,000 people was 0.076 in Madrid, Spain (2013-2014), 0.075 in Japan (2009) and 0.163 in Australia (2003); prevalence per 10,000 adults was 0.212 in Marshfield, Wisconsin (2003); prevalence per 10,000 children was 0.219 in Saudi Arabia (2004-2005); and birth prevalence (per 10,000 live-births) was 0.252 in Denmark (1994–2014) and Finland (1990-2014), 0.468 in Estonia (2016), 0.448 in Hong Kong (1995-2015), and 0.248 in Western Australia (1953-2003).

CONCLUSIONS: This SLR found that AS prevalence data are few and outdated. Prevalence estimates vary within reference populations, which may be due to variation in study years, geography or study methodology. Recent world-wide data on AS prevalence are needed to corroborate the prevalence estimates currently available.