TANGO2 : expanding the clinical phenotype and spectrum of pathogenic variants

Purpose TANGO2 -related disorders were first described in 2016 and prior to this publication, only 15 individuals with TANGO2 -related disorder were described in the literature. Primary features include metabolic crisis with rhabdomyolysis, encephalopathy, intellectual disability, seizures, and cardiac arrhythmias. We assess whether genotype and phenotype of TANGO2 -related disorder has expanded since the initial discovery and determine the efficacy of exome sequencing (ES) as a diagnostic tool for detecting variants. Methods We present a series of 14 individuals from 11 unrelated families with complex medical and developmental histories, in whom ES or microarray identified compound heterozygous or homozygous variants in TANGO2 . Results The initial presentation of patients with TANGO2 -related disorders can be variable, including primarily neurological presentations. We expand the phenotype and genotype for TANGO2 , highlighting the variability of the disorder. Conclusion TANGO2 -related disorders can have a more diverse clinical presentation than previously anticipated. We illustrate the utility of routine ES data reanalysis whereby discovery of novel disease genes can lead to a diagnosis in previously unsolved cases and the need for additional copy-number variation analysis when ES is performed.