A standard of care for individuals with PIK3CA-related disorders: An international expert consensus statement

Clin Genet. 2022 Jan;101(1):32-47. doi: 10.1111/cge.14027. Epub 2021 Jul 16.


Growth promoting variants in PIK3CA cause a spectrum of developmental disorders, depending on the developmental timing of the mutation and tissues involved. These phenotypically heterogeneous entities have been grouped as PIK3CA-Related Overgrowth Spectrum disorders (PROS). Deep sequencing technologies have facilitated detection of low-level mosaic, often necessitating testing of tissues other than blood. Since clinical management practices vary considerably among healthcare professionals and services across different countries, a consensus on management guidelines is needed. Clinical heterogeneity within this spectrum leads to challenges in establishing management recommendations, which must be based on patient-specific considerations. Moreover, as most of these conditions are rare, affected families may lack access to the medical expertise that is needed to help address the multi-system and often complex medical issues seen with PROS. In March 2019, macrocephaly-capillary malformation (M-CM) patient organizations hosted an expert meeting in Manchester, United Kingdom, to help address these challenges with regards to M-CM syndrome. We have expanded the scope of this project to cover PROS and developed this consensus statement on the preferred approach for managing affected individuals based on our current knowledge.

Keywords: PIK3CA-related overgrowth spectrum; clinical management; expert consensus; mosaic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Class I Phosphatidylinositol 3-Kinases / genetics*
  • Consensus Development Conferences as Topic
  • Diagnosis, Differential
  • Disease Management
  • Genetic Association Studies* / methods
  • Genetic Predisposition to Disease*
  • Genetic Testing
  • Growth Disorders / diagnosis
  • Growth Disorders / genetics
  • Growth Disorders / therapy
  • Humans
  • Phenotype
  • Prenatal Diagnosis
  • Standard of Care*


  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human