PIK3CA-related overgrowth spectrum (PROS) is an

umbrella term In linguistics, semantics, general semantics, and ontologies, hyponymy () is a semantic relation between a hyponym denoting a subtype and a hypernym or hyperonym (sometimes called umbrella term or blanket term) denoting a supertype. In other ...

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 m ...

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__

PROS spectrum diseases

PROS spectrum diseases include: * Fibro-adipose vascular anomaly * Hemihyperplasia–multiple lipomatosis syndrome * CLOVES syndrome *

Macrodactyly Local gigantism or localised gigantism is a condition in which a certain part of the body acquires larger than normal size due to excessive growth of the anatomical structures or abnormal accumulation of substances. It is more common in fingers an ...

* Facial infiltrating lipomatosis *

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

* Dysplastic megalencephaly * Klippel–Trénaunay syndrome

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 can be used to treat vascular malformations. 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