Background: The Central Registry of Rare Diseases (CRRD) underpins Belgium’s national surveillance infrastructure for rare diseases. This study characterises the registered population between 2015 and 2025, describing diagnostic pathways, referral patterns, and coding practices. The registry generates evidence to support epidemiological surveillance, research, health system organisation, and policy.

Methods: The CRRD is a national, population-based registry collecting a minimal, pseudonymised dataset from patients with confirmed rare disease diagnoses seen at accredited genetic centres in Belgium. Data are captured once at diagnosis without longitudinal follow-up, reflecting a cross-sectional design. Data collection follows EU Rare Diseases Platform common data elements and Orphanet nomenclature (ORPHAcodes), supporting interoperability and harmonised reporting.

Results: After validation and data cleaning, 9,551 unique patients were included. Disease onset occurred frequently prenatally or during childhood. Median diagnostic delay ranged from 1.5 to 1.7 years, varying across disease groups. Referrals originated mainly from medical specialists (79.4%), followed by patient-initiated referrals (10.9%) and general practitioners (5.6%). ORPHAcodes were used in 70.2% of registrations, representing 1,423 distinct diagnoses. Marked heterogeneity in clinical data completeness and coding practices underscores the intrinsic complexity of rare disease documentation and the critical need for harmonisation across electronic health record systems.

Conclusion: The CRRD provides a structured baseline for rare disease surveillance and insight into diagnostic and referral patterns in Belgium. However, it is not yet fully representative of national prevalence, as findings reflect activity only within participating centres. Limitations include incomplete coverage, heterogeneous disease coding and missing or inconsistent data. Ongoing expansion to additional data providers and strengthened governance, including mandatory registration under the second Belgian Plan for Rare Diseases (2026–2030), are expected to enhance representativeness, harmonisation, and interoperability, supporting the CRRD’s role as a digital infrastructure for evidence-informed care planning and policy development and evaluation.