Diagnostic delay in monogenic disease: A scoping review.

Purpose: Diagnostic delay in monogenic disease is reportedly common. We conducted a scoping review investigating variability in study design, results, and conclusions.

Methods: We searched the academic literature on January 17, 2023, for original peer reviewed journals and conference articles that quantified diagnostic delay in monogenic disease. We abstracted the reported diagnostic delay, relevant study design features, and definitions.

Results: Our search identified 259 articles quantifying diagnostic delay in 111 distinct monogenetic diseases. Median reported diagnostic delay for all studies collectively in monogenetic diseases was 5.0 years (IQR 2-10). There was major variation in the reported delay within individual monogenetic diseases. Shorter delay was associated with disorders of childhood metabolism, immunity, and development. The majority (67.6%) of articles that studied delay reported an improvement with calendar time. Study design and definitions of delay were highly heterogenous. Three gaps were identified: (1) no studies were conducted in the least developed countries, (2) delay has not been studied for the majority of known, or (3) most prevalent genetic diseases.

Conclusion: Heterogenous study design and definitions of diagnostic delay inhibit comparison across studies. Future efforts should focus on standardizing delay measurements, while expanding the research to low-income countries.