Somatic Overgrowth and Vascular Anomalies
Working Group Charter
Best Practices in Diagnostic Testing for Disorders of Somatic Overgrowth and Vascular Anomalies
Work Product Category
Manuscript or Publication: Practice guideline/Review of genetic/genomic abnormalities and their clinical significance
Specific Aims for the Work Product
Propose Best Practices and Guidelines for Genetic Testing and Clinical Management of individuals with Vascular Anomalies and/or Overgrowth Disorders
Guidelines for classification of somatic variants in genes associated with Vascular Anomalies and/or Overgrowth Disorders
Vascular anomalies and overgrowth disorders are typically caused by variants that occur in only a subset of cells, attributed to mosaicism. Due to the mosaic occurrence of these variants, they are poorly detected in blood, necessitating sensitive assays to detect them in affected tissues. We will perform a comprehensive literature review of current testing practices, compare testing practices in four academic medical centers (University of Washington in St. Louis, Seattle Children’s Hospital, Nationwide Children’s Hospital, and Children’s Hospital Los Angeles) and propose evidence-based guidelines for optimal diagnosis of vascular anomalies and overgrowth disorders. Additionally, we will review recurrent and major classes of genomic aberrations in the different types of vascular malformations.
Current ACMG/AMP variant classification guidelines focus on germline conditions, and AMP/ASCO/CAP guidelines focus on variant classification in cancer. While specific guidelines for somatic variants in the genes AKT3, MTOR, PIK3CA, and PIK3R2 associated with brain malformations have recently been published by ClinGen, general guidelines for somatic variants in vascular and overgrowth disorders are lacking and will be addressed in this aim.
Working Group Members
Yang Cao
Washington University in St. Louis
Avinash V. Dharmadhikari
Children’s Hospital Los Angeles
Denise Adams
Children's Hospital of Philadelphia
Catherine Cottrell
Nationwide Children's Hospital
Adrienne Hammill
Cincinnati Children’s Hospitalof Texas MD Anderson Cancer Center
Patricia Hernandez
Washington University in St. Louis
Claire Hou
Nationwide Children's Hospital
Katherine King
Washington University
Jie Liu
Cincinnati Children's Hospital
Bahareh Majored
BC Cancer
Candace Myers
Seattle Children’s Hospital
Thuy Phung
University of South Alabama
Lea F. Surry
Children's Hospital of Philadelphia
Cate Paschal
Seattle Children’s Hospital