Genome Sequencing Improves Diagnosis for Rare Pediatric Diseases: A Meta-Analysis of Diagnostic Yield and Clinical Utility of Genome and Exome Sequencing in Pediatric Rare and Undiagnosed Genetic Diseases
Rajshree Pandey, Noemi Fluetsch Brennan, Kalliopi Trachana, Sarah Katsandres, Olaf Bodamer, John Belmont, David L. Veenstra, Siyang Peng
In this newly published paper, David Veenstra, Noemi F. Brennan, and Sarah Katsandres of Curta, along with colleagues from Illumina, conducted a systematic literature review and meta-analysis to evaluate the diagnostic yield and clinical utility of genome sequencing (GS) and exome sequencing (ES) in pediatric populations with rare and undiagnosed genetic diseases.
The authors identified 108 studies including a total of 24,631 probands with diverse clinical indications. They found that among the highest quality studies, the odds of diagnosis using GS were 1.7-times that of ES. The authors also evaluated clinical utility – the proportion of patients whose clinical management changed following a confirmed genetic diagnosis. A third of the studies reported clinical utility and found similar rates among GS and ES (58.7% vs. 54.5%, respectively).
This meta-analysis expands upon prior work by Clark et al. and aimed to close an important gap in evidence by evaluating the diagnostic yield and clinical utility of GS and ES among clinical indication subgroups, which previously hadn’t been done in pediatric populations alone. Notably, this study is the first to evaluate the diagnostic yield of first-line GS use specifically, offering valuable insight into early genetic testing in the diagnostic journey of children with rare genetic diseases.
These findings will be important for clinical decision-making: the increase in clinical value of genome-wide sequencing over the standard of care testing translates to more patients benefiting from personalized medical management, and sooner in their care journey.