Genotyping as Part of Routine Clinical Care-The Outcomes for a Large Paediatric Vascular Anomaly Cohort

Abstract

We describe the phenotypic and genotypic spectrum of patients with vascular anomaly (VA) in a paediatric multi-disciplinary VA clinic. We measured the clinical utility of genotyping by comparing pre and posttest diagnosis and management. A 46-month retrospective analysis occurred for 250 patients offered genetic testing in the VA clinic. DNA was extracted from biopsied vascular lesions. The coding regions of 27 genes were amplified by multiplex PCR and sequenced with mean coverage depth ranging from 3005× to 66,320×, achieving >95% amplification with at least 500 reads. The limit of detection was approximately 1%. Germline confirmatory testing was arranged where phenotype and variant allele frequency (AF) were compatible with a heritable VA. A molecular diagnosis was identified for 191 of 250 (76%). A somatic cause for VA was confirmed for 70% and a germline cause for 6%. Genetic testing supported the clinical diagnosis for 55% of our patient group and revised the clinical diagnosis for 21%. For patients with a revised clinical diagnosis, a management change occurred for 62%. 33% of patients offered genetic testing for VA had a management change. 24% were referred for consideration of molecularly targeted therapy (MTT). Routine genotyping in paediatric VA improves diagnosis and management outcomes.