OBJECTIVES: Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by loss of UBE3A expression in neurons. Patients present with intellectual disability, balance disorder, behavioral issues, seizures, sleep disturbances, and speech impairment. The most common genetic cause is a deletion on chromosome 15q11-q13 encompassing the UBE3A gene, accounting for about 70% of cases. Other causes include pathogenic variants in UBE3A, imprinting defects (ID), and paternal uniparental disomy (UPD) for chromosome 15, collectively known as non-deletion AS. To identify comprehensive evidence of the impact of AS on patients’ quality of life (QoL).

METHODS: We systematically searched Embase^® and MEDLINE^® via Embase.com to identify English-language articles reporting QoL data for AS in children and adults.

RESULTS: Among the 69 records screened, 13 studies were included. Data were mostly reported for the US and the Netherlands. The Aberrant Behavior Checklist-Community version (ABC-C) and Infant and Toddler Quality of Life Questionnaire–Short Form (ITQOL-SF47) were the most widely administered QoL scales. The EQ-5D data indicated that patients’ self-care, mobility, and daily activities were most impacted. Participants with non-deletion AS scored an average of 15 points higher on QoL measures compared to those with deletion AS. Additionally, older individuals reported better QoL outcomes, with scores increasing by approximately 1 point per year. The Family Quality of Life (FQoL) questionnaire and ABC-C found significant associations between genotype and sex with various QoL outcomes. Participants with non-deletion genotypes had maladaptive behavior scores that were 4 points lower and reduced parenting stress by 3 points, correlating with a 5-point improvement in family QoL scores.

CONCLUSIONS: AS profoundly impacts QoL through various drivers, including behavioral and emotional problems, sleep disturbances, and genetic factors, highlighting the need for comprehensive, family-centered intervention strategies.