Beyond Single Diagnosis: Exploring Multidiagnostic Realities in Pediatric Patients through Genome Sequencing

Area of Science:

• Genetics
• Genomics
• Rare Diseases

Background:

• Next-generation sequencing has identified multiple genetic diagnoses (MGD).
• Genome sequencing (GS) is the most comprehensive tool but its utility for MGD prevalence is underexplored.

Purpose of the Study:

• To investigate the incidence of single definitive genetic diagnosis (SDD) and MGD in pediatric cases using GS.
• To analyze factors influencing diagnostic yield, including prior testing and patient age.

Main Methods:

• Retrospective analysis of 1487 pediatric cases undergoing GS.
• Categorization of diagnoses into SDD and MGD.
• Statistical analysis of diagnostic yield based on prior testing and age.

Main Results:

• 273 patients (18.4%) received a diagnosis: 245 SDD (16.5%) and 28 MGD (1.9%).
• Prior testing increased MGD yield to 2.7% overall and 14.4% of diagnosed cases.
• Neonates showed the highest diagnostic yield for both SDD (24.5%) and MGD (4.9%).

Conclusions:

• This is the first study exclusively using GS to assess MGD prevalence.
• Findings underscore the complexity of rare diseases and the importance of comprehensive, genome-level diagnostics.
• Accurate diagnosis considering phenotype is crucial for optimal patient management.