Background: Individuals with rare genetic neurodevelopmental disorders are often affected with intellectual disability, psychiatric manifestations, and complex multi-organ comorbidity, necessitating lifelong and multidisciplinary care. Guidelines can offer valuable support in providing evidence-based care for this population, but their development is challenging. Within the European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability ERN-ITHACA, we create guidelines for genetic syndromes and their shared comorbidities, while improving our methodology through evidence reviews and qualitative research involving all stakeholders. Assessment of the nature and quality of existing guidelines is needed to inform future guideline development efforts. 

Methods: We systematically searched MEDLINE, EMBASE, and Orphanet for conditions classified as ‘rare genetic intellectual disability’ (ORPHA:183757) to identify guidelines for rare genetic neurodevelopmental disorders. Methodological quality was assessed using the AGREE (Appraisal of Guidelines, Research, and Evaluation) II tool.

Results: 70 internationally published guidelines, addressing the diagnosis and/or management of 28 conditions, were identified and reviewed. Guidelines generally scored well on the definition of topic and scope, and clarity of recommendations. Most guidelines were developed by multidisciplinary groups. The extent of involvement of paramedical professionals and affected individuals and families varied. The methodological rigour of development was highly variable with limited reporting of literature searches and consensus methods. Reporting of funding sources was inconsistent, and often there was no procedure for managing conflicts of interest. Implementation aspects were given limited attention.

Conclusion: Comprehensive, high-quality guidelines are lacking for many rare neurodevelopmental disorders. Applying rigorous methodology and ensuring applicability are significant challenges in guideline development. This research aims to inform and improve future guideline development processes, contributing to evidence-based care for individuals with rare neurodevelopmental disorders.

Keywords: genetic neurodevelopmental disorders, guidelines, evidence-based care, methodology, rare disease