Rhabdomyolysis in the Era of Next-Generation Sequencing: Selecting Patients with a High Likelihood of a Genetic...

Rhabdomyolysis is a potentially life-threatening condition characterized by acute skeletal muscle breakdown. In addition to well-described external triggers, a genetic contribution is increasingly recognized. We aimed to (I) review the genetic diagnostic approach of rhabdomyolysis, (II) evaluate the clinical characteristics indicative of a genetic susceptibility with the 'RHABDO' acronym, and (III) assess the predictive value of the presence RHABDO features for identifying genetic variants.

In this retrospective two-center study, 122 patients underwent genetic testing for rhabdomyolysis since the introduction of whole exome sequencing (WES) in 2013. The presence of RHABDO features was compared between those with (likely) pathogenic variants and those with benign or no identified variants or variants of uncertain significance.

The testing methods included panel-based WES (82%), Sanger sequencing (49%), and full WES (24%), of which 52 patients (43%) underwent multiple methods. A (likely) pathogenic variant was identified in 13 patients (11%), in all of whom ≥2 RHABDO features were present. The positive predictive value for ≥2 features was 14%, while the negative predictive value was 100%.

These results highlight the relevance of WES in further elucidating the genetic basis of rhabdomyolysis and demonstrated that RHABDO is a valuable tool for selecting patients who should undergo genetic testing.