Cloves syndrome .., (Congenital lipomatous Overgrowth, Vascular malformations, Epidermal nevi, and Skeletal or spinal abnormalities -CLOVES- syndrome) - Gen PIK3CA
Cloves syndrome (Congenital lipomatous Overgrowth, Vascular malformations, and Epidermal nevi, and Skeletal or spinal abnormalities) is characterized by congenital lipomatous overgrowths, complex and combined progressive vascular malformations in the trunk and epidermal nevi. Patients also exhibit an abnormal and disproportionate distribution of the adipose tissue. This syndrome may be associated with scoliosis and variable gravity bone structures enlarged without progressive bone overgrowth. The presence of scoliotic demonstrations has led to suggestions expanding the acronym for the disease Cloves. In contrast to bone abnormalities characteristic of Proteus syndrome, abnormalities in the syndrome Cloves occur only after major surgery. They have been described occasionally central nervous system manifestations (generalized seizures, hemimegalencephaly, dysgenesis callosum and neuronal migration defects) and head asymmetry.
In 2012 , 11 individuals with progressive segmental overgrowth syndrome were described. The main characteristic was the overgrowth of subcutaneous, muscular and visceral fibrofatty tissue with skeletal overgrowth. Seven of 8 patients had congenital overgrowth. History all had a wide range of variability, although none of the affected individuals had developed malignant tumors, and one patient had nephrogenic remains benign.
3 mutations have been identified in PIK3CA gene amino acids, (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), located on the long arm of chromosome 3 (3q26.3). This gene encodes the p110 protein, a subunit of the enzyme phosphatidylinositol 3-kinase (PI3K). The p110 catalytic subunit protein is because performing the action of PI3K, while the other subunit (encoded by a different gene), regulates the activity of the enzyme. Like other kinases, PI3K add a phosphate group to other proteins through phosphorylation. PI3K enzyme plays a role in chemical signaling within cells. PI3K signaling is important for many cellular activities, including cell growth and proliferation, cell migration, the coding of new proteins, the transport of substances within the cells, and cell survival. These functions are important for the development of tissues throughout the body, including the brain and blood vessels. It is believed that PI3K signaling may be involved in the regulation of various hormones and may play a role in the maturation of adipocytes.
It appears that the syndrome Cloves is due to activating mutations postzygotic in the PIK3CA gene, and the hypothesis that a low rate of malignant transformation in patients with this syndrome appears, is due to low level expression PIK3CA endogenous in most cells. It has also been identified somatic mosaicism for a PIK3CA mutation in 3 patients who had been diagnosed with Klippel-Trenaunay-Weber syndrome Overgrowth similar to those of Clove syndrome features.
Tests in IVAMI: in IVAMI perform detection of mutations associated with syndrome Cloves, by complete PCR amplification of the PIK3CA gene exons and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).