Prioritizing topics for a clinical practice guideline on SATB2-associated syndrome: methodological rigor vs clinical usability

SATB2-associated syndrome (SAS) is a rare genetic condition that causes developmental delays and other characteristic features. A new clinical practice guideline (CPG) for SAS is currently being developed by the European Reference Network ITHACA, together with families, caregivers, and health-care professionals. To make sure the guideline focuses on the most important needs of the SAS community, a structured process was used to decide which clinical topics should be included. First, families across the SAS community were asked to share their concerns. This resulted in 376 topics, which were combined into 48 broader clinical themes. Next, 269 people completed an online survey to rank these topics. Most respondents were family members or caregivers, and some were clinicians. Finally, the guideline development team reviewed the results and discussed which topics should be prioritized. Although the original goal was to select 12 questions to answer through systematic reviews, the team decided that limiting the guideline to only 12 topics would leave out important issues. Instead, they agreed on 22 key questions, which would be addressed with only 1 systematic review. The CPG recommendations would then be more complete but supported with less systematically searched evidence. This experience highlights an ongoing challenge in rare disease guideline development: balancing completeness and practicality with strict methodological standards.