Expanding the Phenotype of SETD5-Related Disorder Through a Facebook Support Group

Background: SETD5-related disorder is a neurodevelopmental condition caused by pathogenic variants in the SETD5 gene. Reported features include intellectual disability, developmental delay, autism spectrum disorder, feeding difficulties, hypotonia, and dysmorphic facial features. The disorder was first described in 2014 with fewer than 75 reported cases in the literature to date. Given its rarity, affected families often turn to online communities for information and support. Previous studies have highlighted the growing role of social media platforms, such as Facebook, in connecting and supporting families impacted by rare disorders. This study surveyed members of a SETD5-related disorder Facebook support group to expand the phenotypic spectrum and describe users’ experiences of the online community. Methods: A descriptive online study was distributed between August and November 2024 to members of a Facebook support group for SETD5-related disorder. Participants completed a Research Electronic Data Capture survey assessing medical features, disorder-related challenges, and perceived utility of group membership. Quantitative data were analyzed using descriptive statistics and two-sample proportion tests in Microsoft Excel and Stata. Qualitative data were thematically coded. Results: Fifty-one members from 12 countries responded. Among affected individuals, 80% were under 18 years, and the mean age at diagnosis was 9.2 years. Common features included developmental delay (96%), hypotonia (78%), intellectual disability (75%), gait abnormality (59%), vision problems (51%), constipation (47%), and anxiety (47%). Potential novel findings included high pain tolerance (43%), persistent leg pain (31%), and joint pain (27%). Conclusions: Facebook group participation empowered families through shared experiences and information exchange. Findings expand the phenotypic spectrum and inform prognosis, surveillance, and management.