Pediatric medicine advances further with the utilization of genomic medicine

The innovation in the diagnosis of pediatric diseases brought by genomic medicine

Traditionally, genetic diseases in children were diagnosed by identifying candidate diseases based on family history, clinical symptoms, and laboratory findings, confirming each causative gene or region one by one, and integrating the results. In the cases with rare disease, it was difficult to narrow down the differential diagnosis, often resulting in an unidentified cause. In recent years, early diagnosis has become possible through the comprehensive identification of partial chromosomal deletions and genetic sequence abnormalities, and confirmation that the results are consistent with clinical symptoms. Techniques such as chromosomal microarray analysis and next-generation sequencing have been used for this comprehensive analysis. (Fig. 1).

Microarray analysis and next-generation sequencing

In October 2021, microarray testing, which involves competitively hybridizing DNA to probes attached to a glass slide, became covered by insurance. This technology can detect copy number variations with high resolution, enabling the detection of subtle deletions and duplications across the entire genome that could not be identified through karyotype analysis. Additionally, next-generation sequencers, which can rapidly and massively decode gene sequences, have been implemented, allowing for whole-exome analysis under the Undiagnosed Disease Initiative (IRUD) since 2015. Tokushima University has been actively involved in this initiative as an IRUD hub hospital. Approximately 60% of participating undiagnosed patients have received a diagnosis (Figs. 2 and 3).

Early diagnosis has enabled gene therapy for spinal muscular atrophy and enzyme replacement therapy for congenital metabolic disorders such as Pompe disease. Moving forward, we will continue to leverage genomic medicine to achieve early diagnoses of pediatric diseases, providing peace of mind for families.