PIK3CA-related overgrowth spectrum

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PIK3CA-related overgrowth spectrum (PROS) is an umbrella term for rare syndromes characterized by malformations and tissue overgrowth caused by somatic mutations in PIK3CA gene. [1] [2] [3] In PROS diseases individual malformations are seen in several different tissues such as skin, vasculature, bones, fat and brain tissue depending on the specific disease.

Contents

Diseases

PIK3CA-related overgrowth spectrum diseases include:

Pathophysiology

PIK3CA gene codes for p110α protein which is a catalytic subunit of phosphoinositide 3-kinase, a major regulator of several important cellular functions such as cell proliferation, growth and apoptosis. [4] Mutations in PIK3CA cause over-activity of PI3K which in turn leads to altered growth of cells and tissues which is thought to be important for overgrowth and malformations in PROS. [5] Different presentations of PROS diseases are likely explained by acquisition of the mutation in different time points and different cell types during embryonic development [5]

Treatment

Treatment of PROS diseases is variable and depends on the specific disease. Curative treatment does not exist and most treatments are given to control symptoms. Overgrowth and malformations of solid tissues can be treated with surgery. Sclerotherapy can be used to treat vascular malformations. [5] In CLOVES syndrome experimental medical therapy using PIK3CA inhibitor, BYL719, has been reported to be effective to relieve pain and diminish the malformations. [6]

References

  1. ↑ "PIK3CA-related overgrowth spectrum". rarediseases.info.nih.gov. National Institute of Health. Archived from the original on 2018-08-02. Retrieved 2018-10-03.
  2. ↑ Keppler-Noreuil, Kim M.; Rios, Jonathan J.; Parker, Victoria E. R.; Semple, Robert K.; Lindhurst, Marjorie J.; Sapp, Julie C.; Alomari, Ahmad; Ezaki, Marybeth; Dobyns, William (2014-12-24). "PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation". American Journal of Medical Genetics. Part A. 167A (2): 287–295. doi:10.1002/ajmg.a.36836. ISSN   1552-4833. PMC   4480633 . PMID   25557259.
  3. ↑ "Classification | International Society for the Study of Vascular Anomalies". issva.org. Archived from the original on 2018-03-29. Retrieved 2018-09-23.
  4. ↑ Fruman, David A.; Chiu, Honyin; Hopkins, Benjamin D.; Bagrodia, Shubha; Cantley, Lewis C.; Abraham, Robert T. (2017-08-10). "The PI3K Pathway in Human Disease". Cell. 170 (4): 605–635. doi:10.1016/j.cell.2017.07.029. ISSN   1097-4172. PMC   5726441 . PMID   28802037.
  5. 1 2 3 Madsen, Ralitsa R.; Vanhaesebroeck, Bart; Semple, Robert K. (2018-09-06). "Cancer-Associated PIK3CA Mutations in Overgrowth Disorders" (PDF). Trends in Molecular Medicine. 24 (10): 856–870. doi:10.1016/j.molmed.2018.08.003. ISSN   1471-499X. PMC   6185869 . PMID   30197175.
  6. ↑ Venot, Quitterie; Blanc, Thomas; Rabia, Smail Hadj; Berteloot, Laureline; Ladraa, Sophia; Duong, Jean-Paul; Blanc, Estelle; Johnson, Simon C.; Hoguin, Clément (2018-06-13). "Targeted therapy in patients with PIK3CA-related overgrowth syndrome". Nature. 558 (7711): 540–546. Bibcode:2018Natur.558..540V. doi:10.1038/s41586-018-0217-9. ISSN   1476-4687. PMC   7610773 . PMID   29899452. S2CID   49189779.
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