PIK3CA-related overgrowth spectrum
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 individuals malformations are seen in several different tissues such as skin, vasculature, bones, fat and brain tissue depending on the specific disease.
PROS spectrum diseases
PROS spectrum diseases include:
- Fibro-adipose vascular anomaly
- Hemihyperplasia–multiple lipomatosis syndrome
- CLOVES syndrome
- Macrodactyly
- Facial infiltrating lipomatosis
- Macrocephaly-capillary malformation
- Dysplastic megalencephaly
- Klippel–Trénaunay syndrome
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
- ^ "PIK3CA-related overgrowth spectrum". rarediseases.info.nih.gov. National Institute of Health. Archived from the original on 2018-08-02. Retrieved 2018-10-03.
- ^ 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.
- ^ "Classification | International Society for the Study of Vascular Anomalies". issva.org. Archived from the original on 2018-03-29. Retrieved 2018-09-23.
- ^ 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.
- ^ a b c 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.
- ^ 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.