Related Experiment Video
Updated: Jun 3, 2025
A Patient-Derived Xenograft Model for Venous Malformation
Published on: June 15, 2020
Genotyping as Part of Routine Clinical Care-The Outcomes for a Large Paediatric Vascular Anomaly Cohort
Sinead O'Sullivan1, Maria Shilova2,3, Angharad Webb4
1Genetic Health Queensland, Royal Brisbane and Women's Hospital, Herston, Australia.
Insights
Routine genetic testing in pediatric vascular anomalies (VA) significantly improves diagnosis and management. Identifying the cause, whether somatic or germline, guides treatment and aids in considering molecularly targeted therapies.
Area of Science:
- Genetics
- Pediatrics
- Vascular Biology
Background:
- Vascular anomalies (VA) present a complex diagnostic challenge in pediatric patients.
- A multidisciplinary approach is crucial for managing diverse VA cases.
- Genotyping offers potential for improved diagnostic accuracy and treatment strategies.
Purpose of the Study:
- To evaluate the phenotypic and genotypic spectrum of pediatric patients with vascular anomalies.
- To assess the clinical utility and impact of genetic testing on diagnosis and management.
- To determine the frequency of somatic and germline causes of VA.
Main Methods:
- Retrospective analysis of 250 pediatric patients over 46 months in a VA clinic.
- DNA extraction from vascular lesions followed by multiplex PCR and sequencing of 27 genes.
- Analysis of variant allele frequency (AF) and germline confirmatory testing.
Main Results:
- A molecular diagnosis was achieved in 76% (191/250) of patients.
- Somatic causes accounted for 70% and germline causes for 6% of VAs.
- Genetic testing supported or revised the clinical diagnosis in 76% of cases, leading to management changes in 33% and referral for molecularly targeted therapy (MTT) in 24%.
Conclusions:
- Routine genotyping in pediatric vascular anomalies enhances diagnostic precision.
- Genetic testing directly impacts patient management and treatment decisions.
- This approach facilitates the consideration of targeted therapies for improved outcomes.
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.
Related Concept Videos
01:11Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
01:35Pedigree Analysis