Expanding the Phenotype of SETD5-related Disorder through a Facebook Support Group

SETD5-related disorder is a neurodevelopmental disorder caused by pathogenic variants in the SETD5 gene, impacting brain function. SETD5-related disorder was discovered in 2014, with fewer than 75 individuals reported to-date in the literature. This study aims to expand the phenotypic spectrum of SETD5-related disorder and describe the experiences of using an online support group. Fifty-one members of a Facebook group specific to individuals and family members affected by SETD5-related disorder were surveyed about medical features, disorder-related challenges, and utility of the Facebook group membership. The most common medical features of SETD5-related disorder identified were developmental delay (96%), hypotonia (78%), intellectual disability (75%), gait abnormality (59%), vision problems (51%), frequent constipation (47%), and anxiety (47%) (p< 0.001). Our findings elucidated novel phenotypes–joint pain (27%) and persistent leg pain (31%)–and higher prevalence of seizures (25%). We found that SETD5-related disorder is best characterized heterogeneously by developmental delays, musculoskeletal, head-eyes-ears-nose-throat, neurological, and gastrointestinal problems. Our data represented individuals from 12 different countries and illustrated how Facebook group members felt empowered and informed by the online support group. Ultimately, our findings aim to provide additional clinical information to support SETD5-related disorder’s diagnostic criteria and offer prognostic insights for families and healthcare providers.