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<ref>

PIK3CA-related overgrowth spectrum(link). rarediseases.info.nih.gov. National Institute of Health.

Accessed 2018-10-03.

</ref><ref>Keppler-Noreuil, Kim M.,

 PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation, 
 American Journal of Medical Genetics. Part A, 
 
 Vol. 167A(Issue: 2),
 pp. 287–295,
 DOI: 10.1002/ajmg.a.36836,
 PMID: 25557259,
 PMC: 4480633,</ref><ref>

Classification | International Society for the Study of Vascular Anomalies(link). issva.org.

Accessed 2018-09-23.

</ref>. 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 include:

• Fibroadipose hyperplasia or Overgrowth
• Hemihyperplasia Multiple Lipomatosis
• Congenital Lipomatous Overgrowth
• Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal (CLOVES) syndrome
• Macrodactyly
• Facial Infiltrating Lipomatosis
• Megalencephaly - Capillary Malformation
• Dysplastic Megalencephaly
• Klippel-Trenaunay 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.<ref>Fruman, David A.,

 The PI3K Pathway in Human Disease, 
 Cell, 
 
 Vol. 170(Issue: 4),
 pp. 605–635,
 DOI: 10.1016/j.cell.2017.07.029,
 PMID: 28802037,
 PMC: 5726441,</ref>. 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<ref name="Madsen 2018">Madsen, Ralitsa R., 
 Cancer-Associated PIK3CA Mutations in Overgrowth Disorders, 
 Trends in Molecular Medicine, 
 
 Vol. 24(Issue: 10),
 pp. 856–870,
 DOI: 10.1016/j.molmed.2018.08.003,
 PMID: 30197175,
 PMC: 6185869,
 
 Full text,</ref>. Different presentations of PROS diseases are likely explained by acquisition of the mutation in different time points and different cell types during embryonic development <ref name="Madsen 2018" />

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<ref name="Madsen 2018" />. In CLOVES syndrome experimental medical therapy using PIK3CA inhibitor, BYL719, has been reported to be effective to relieve pain and diminish the malformations<ref>Venot, Quitterie,

 Targeted therapy in patients with PIK3CA-related overgrowth syndrome, 
 Nature, 
 
 Vol. 558(Issue: 7711),
 pp. 540–546,
 DOI: 10.1038/s41586-018-0217-9,
 PMID: 29899452,</ref>. 

References

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