Whole genome sequencing provides modest diagnostic gains in pediatric movement disorders

Short-read whole genome sequencing (srWGS) offers limited additional diagnostic value in pediatric movement disorders, as most cases are resolved at the exome level, however, it can uncover unique findings in a small subset of patients, according to a presentation at the 53rd Child Neurology Society Annual Meeting.

Researchers studied 43 children with unclear etiologies despite prior genetic testing.

Using the Illumina NovaSeq platform, researchers analyzed srWGS data and identified genetic diagnoses in 37.2% of cases. In addition, candidate genes were proposed in 34.9% of patients. Spasticity was the most common symptom, affecting 72.1% of participants, followed by ataxia (58.1%) and dystonia (55.8%).

Although 86.1% of participants had previously undergone clinical genetic testing, srWGS offered additional diagnostic insights in 11.6% of cases. Notable findings included specific genetic variations: a repeat expansion in the HTT gene, a duplication in the MECP2 gene, and an ALU-insertion in the ATM gene. In addition, potential large-scale DNA changes known as candidate copy number variations were detected in 4.7% of cases.

Reference
Schierbaum L, et al. Additional diagnostic yield of short-read whole genome sequencing in childhood-onset movement disorders: a one-year follow-up study. Presented at: 53rd Child Neurology Society Annual Meeting; 2024; Boston, MA.