PIK3CA-related overgrowth spectrum (PROS) is an

umbrella term Hypernymy and hyponymy are the wikt:Wiktionary:Semantic relations, semantic relations between a generic term (''hypernym'') and a more specific term (''hyponym''). The hypernym is also called a ''supertype'', ''umbrella term'', or ''blanket term ...

for rare syndromes characterized by malformations and tissue overgrowth caused by

somatic mutation A somatic mutation is a change in the DNA sequence of a somatic cell of a multicellular organism with dedicated reproductive cells; that is, any mutation that occurs in a cell other than a gamete, germ cell, or gametocyte. Unlike germline muta ...

s in PIK3CA gene. 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. __TOC__

Diseases

PIK3CA-related overgrowth spectrum diseases include: * Fibro-adipose vascular anomaly *

Hemihyperplasia–multiple lipomatosis syndrome Hemihyperplasia–multiple lipomatosis syndrome is a cutaneous condition characterized by multiple lipomas in association with asymmetric (but non-progressive and non-distorting) overgrowth, cutaneous capillary malformations, and thickened plantar ...

* CLOVES syndrome * Macrodactyly * Facial infiltrating lipomatosis *

Macrocephaly-capillary malformation Macrocephaly-capillary malformation (M-CM) is a multiple malformation syndrome causing abnormal body and head overgrowth and cutaneous, Blood vessel, vascular, neurologic, and limb abnormalities. Though not every patient has all features, commonl ...

* Dysplastic megalencephaly *

Klippel–Trénaunay syndrome Klippel–Trénaunay syndrome, formerly Klippel–Trénaunay–Weber syndrome and sometimes angioosteohypertrophy syndrome and hemangiectatic hypertrophy, is a rare congenital medical condition in which blood vessels and/or lymph vessels fail to f ...

Pathophysiology

PIK3CA gene codes for p110α protein which is a catalytic subunit of

phosphoinositide 3-kinase Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which i ...

, a major regulator of several important cellular functions such as cell proliferation, growth and apoptosis. 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. Different presentations of PROS diseases are likely explained by acquisition of the mutation in different time points and different cell types during embryonic development

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 Sclerotherapy (the word reflects the Greek ''skleros'', meaning ''hard'') is a procedure used to treat blood vessel malformations ( vascular malformations) and also malformations of the lymphatic system. A medication is injected into the vessels ...

can be used to treat

vascular malformation A vascular malformation is a type of vascular anomaly. They may cause aesthetic problems as they have a growth cycle, and can continue to grow throughout life. Vascular malformations of the brain include those involving capillaries, and those in ...

s. In CLOVES syndrome experimental medical therapy using PIK3CA inhibitor, BYL719, has been reported to be effective to relieve pain and diminish the malformations.

References

{{reflist Rare syndromes