Sturge-Weber syndrome (SWS) - GNAQ gene

Sturge-Weber syndrome (SWS), also known as encephalofacial hemangiomatosis syndrome or neuroretinoangiomatosis, is a process that affects the development of certain blood vessels, leading to abnormalities in the brain, skin and eyes. This syndrome is characterized by three main characteristics: port-wine stain (capillary malformation), leptomeningeal angioma and glaucoma. However, not all people with SWS have these three characteristics.

Leptomeningeal angioma can alter blood flow in the brain, and lead to atrophy and calcifications in the brain below the angioma. This decrease in blood flow due can also cause stroke. Frequently, these episodes involve hemiparesis, vision abnormalities, seizures (usually focal) and migraines. In affected individuals, manifestations usually begin at 2 years. People with SWS have different levels of cognitive function, ranging from normal intelligence to intellectual disability.

Glaucoma in SWS usually develops in childhood or early adulthood and can cause vision impairment and buftalmos. In addition, individuals affected by this process may present with hemangiomas in various parts of the eye.

This syndrome is due to a mutation in the GNAQ gene (G protein subunit alpha q), located on the long arm of chromosome 9 (9q21.2), which encodes the Gαq protein. The Gαq protein is part of the trimeric G protein complex. When the protein complex binds to a receptor, the Gαq protein binds to a GTP molecule and is activated. The activated Gαq protein is then separated from the protein complex and activates the signaling pathways that help regulate the development and function of blood vessels. The Gαq protein converts GTP into the GDP molecule, which inactivates the protein. It is then reattached to the trimeric protein complex, deactivating the signaling pathways.

At least one mutation in the GNAQ gene has been identified in individuals with this syndrome that substitutes the amino acid arginine for the amino acid glutamine at position 183 in the Gαq protein (Arg183Gln or R183Q). After activation, the altered Gαq protein cannot convert GTP to GDP. As a consequence, the protein is always active and the signaling pathways controlled by it are constantly activated. This increase in signaling probably disrupts the regulation of blood vessel development, leading to abnormal and excessive vessel formation before birth.

Sturge-Weber syndrome is not inherited. The mutation that leads to the development of this process is somatic, which means that it occurs after fertilization. It is believed that the mutation occurs in a cell at the beginning of development before birth. As that cell continues to grow and divide, cells derived from it, specifically in certain cells of the brain, eyes and skin that participate in the formation of blood vessels, also have the mutation, while other cells in the body do not they have This situation is called mosaicism.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with Sturge-Weber syndrome, by means of the complete PCR amplification of the exons of the GNAQ gene, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leukocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).