Sturge-Weber syndrome is a rare, neurological disorder present at birth and characterized by a port-wine stain birthmark on the forehead and upper eyelid on one side of the face. The birthmark can vary in color from light pink to deep purple and is caused by an overabundance of capillaries (small blood vessels) around the trigeminal nerve just beneath the surface of the face.

Sturge-Weber syndrome is also accompanied by abnormal blood vessels on the brain's surface and the loss of tissue (atrophy) with deposits of calcium (calcification) in the cerebral cortex of the brain on the same side as the birthmark. Sturge-Weber syndrome rarely affects other body organs.

Neurological symptoms may include:

• Seizures that begin in infancy and may worsen with age. Convulsions usually happen on the side of the body opposite the birthmark and vary in severity
• Intermittent or permanent muscle weakness
• Developmental delays and cognitive impairment
• Glaucoma (increased pressure within the eye) at birth or later. The increased pressure within the eye can cause the eyeball to enlarge and bulge out of its socket (buphthalmos)
• Migraines

Treatment is symptomatic. Laser treatment may be used to lighten or remove the birthmark. Anticonvulsant medications may be used to control seizures. Physical therapy may help with muscle weakness and educational therapy may help those with impaired cognition or developmental delays. Doctors recommend yearly monitoring for glaucoma.

Although it is possible for the birthmark and atrophy in the cerebral cortex to be present without symptoms, most infants will develop convulsive seizures during their first year of life. There is a greater likelihood of intellectual impairment when seizures start before the age of 2 and are resistant to treatment.

Sturge-Weber syndrome is caused by a mutation in the GNAQ gene. This gene provides instructions for making a protein called guanine nucleotide-binding protein G(q) subunit alpha (Gαq). The Gαq protein is part of a group of proteins (complex) that regulates signaling pathways to help control the development and function of blood vessels.

The GNAQ gene mutation that causes Sturge-Weber syndrome results in the production of a protein with impaired function. As a result, the altered Gαq protein cannot play its part in regulating signaling pathways, resulting in abnormally increased signaling. The enhanced signaling likely disrupts the regulation of blood vessel development, causing abnormal and excessive formation of vessels before birth in people with Sturge-Weber syndrome.

Normal Function

The GNAQ gene provides instructions for making a protein called guanine nucleotide-binding protein G(q) subunit alpha (Gαq). The Gαq protein is part of a group of proteins called the trimeric G protein complex. This complex attaches (binds) to other proteins called G protein coupled receptors. When the protein complex is bound to a receptor, the Gαq protein binds to a molecule called GTP and is turned on (activated). The activated Gαq protein then separates from the protein complex and activates signaling pathways that help to regulate the development and function of blood vessels. The Gαq protein converts GTP to a similar molecule called GDP, which turns off (inactivates) the protein. It then reattaches to the trimeric G protein complex, turning off the signaling pathways.

Health Conditions Related to Genetic Changes

Sturge-Weber syndrome

At least one mutation in the GNAQ gene has been found to cause Sturge-Weber syndrome. Sturge-Weber syndrome is a condition that affects the development of certain blood vessels and often leads to three major features: a red or pink birthmark called a port-wine birthmark, brain abnormalities, and increased pressure in the eye (glaucoma) or other eye problems. The GNAQ gene mutation associated with Sturge-Weber syndrome changes a single building block (amino acid) in the Gαq protein. It replaces the amino acid arginine with the amino acid glutamine at position 183 in the Gαq protein (written as Arg183Gln or R183Q). This mutation is not inherited but occurs after conception. This alteration is called a somatic mutation and is present only in certain cells, specifically cells in the brain, eyes, and skin that are involved in blood vessel formation.

Following its activation, the altered Gαq protein cannot convert GTP to GDP. As a result, the protein is always active, and signaling pathways controlled by it are constantly turned on. This increased signaling likely disrupts the regulation of blood vessel development, causing abnormal and excessive formation of vessels before birth in people with Sturge-Weber syndrome.

Other disorders

The R183Q mutation in the GNAQ gene can also cause port-wine birthmarks without the brain or eye abnormalities that are often associated with Sturge-Weber syndrome (described above). As in Sturge-Weber syndrome, isolated port-wine birthmarks caused by a GNAQ gene mutation are usually on one side of the face but can be on both sides. It is thought that somatic GNAQ gene mutations that cause isolated port-wine birthmarks occur later in fetal development than those that cause Sturge-Weber syndrome and so affect fewer cells and tissues.

Somatic mutations in the GNAQ gene have also been found in an eye cancer called uveal melanoma. This cancer occurs in the middle layer of the eye called the uvea. The uvea includes the colored portion of the eye (the iris) and related tissues that underlie the white part of the eye (the sclera). The GNAQ gene mutations in uveal melanoma result in an overactive protein, which leads to excessive signaling. This abnormal signaling likely contributes to the overgrowth of cells and to the formation of a cancerous tumor. While the R183Q mutation has been found in uveal melanoma, individuals with Sturge-Weber syndrome or isolated port-wine birthmark do not have an increased risk of this form of cancer. GNAQ gene mutations that lead to uveal melanoma usually occur later in a person's life, typically in adulthood, and are limited to the cells that give rise to the tumor.

Other Names for This Gene

• G-ALPHA-q
• GAQ
• guanine nucleotide binding protein (G protein), q polypeptide
• guanine nucleotide-binding protein alpha-q
• guanine nucleotide-binding protein G(q) subunit alpha

Genomic Location

Sturge-Weber syndrome is not inherited. The mutation that causes this disorder is somatic, which means it occurs after conception. In Sturge-Weber syndrome, the mutation is thought to occur in a cell during early development before birth. As that cell continues to grow and divide, the cells derived from it, specifically certain cells in the brain, eyes, and skin that are involved in blood vessel formation, also have the mutation, while the body's other cells do not. This situation is called mosaicism. The mosaic nature of the mutations helps to explain why the abnormal blood vessel growth occurs in some parts of the body but not in others.