Sturge-Weber syndrome

Definitions & Key takeaways

Sturge-Weber syndrome (SWS) is a rare neurological disorder caused by a mutation of the GNAQ gene and is characterized by the abnormal development of many capillaries in the meninges covering the brain, as well as in some areas of the face innervated by the trigeminal nerve, like the forehead and upper eyelid. The eye on the affected side may also develop glaucoma, with increased pressure in the eye, causing reduced vision or even blindness. There may also be brain atrophy, seizures, and muscle weakness, as well as developmental delay. There is no known cure for SWS, but symptomatic treatment may include anticonvulsants, hemispherectomy to remove the affected portion of the brain, and drugs like latanoprost to manage glaucoma.

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Sturge-Weber syndrome is a congenital neurocutaneous disorder named after William Sturge and Frederick Weber, the first physicians to describe it.
Neurocutaneous because it affects the brain and the skin. In fact, Sturge-Weber syndrome is also called encephalotrigeminal angiomatosis; encephalo- refers to the brain, trigeminal refers to the trigeminal or fifth cranial nerve, and angiomatosis refers to a vascular malformation.
That’s because in Sturge-Weber syndrome there are too many capillaries in the meninges covering the brain, as well as in some areas of the face that are innervated by the trigeminal nerve, like the forehead and upper eyelid.
Finally, in Sturge-Weber syndrome there’s often a congenital mark - a birthmark - called a port-wine stain. When the embryo is one week old, it has two layers of cells: a dorsal or outer epiblast layer and a ventral or inner hypoblast layer.
During week 3 of development the embryo undergoes gastrulation where the cells in the epiblast layer form a three layered trilaminar disc with an ectoderm, mesoderm and endoderm layer.
The ectoderm is the dorsal most germ layer, and through a process called neurulation forms the neural tube. From the neural tube, neural crest cells migrate to help form the central and peripheral nervous systems, as well as the cornea of the eyes and the epidermis layer of the fetal skin.
During week 6 of development, as the cephalic portion of the neural tube grows, a network of tiny blood vessels called a vascular plexus develops, to better supply that neural tissue.
There’s a gene called the GNAQ gene which codes for a guanine nucleotide-binding protein, and that protein is involved in development of the vascular plexus.
Normally, around week 9 of development, the GNAQ gene stops getting expressed, and that leads to regression of the vascular plexus.
In Sturge-Weber syndrome a sporadic mutation occurs in the GNAQ gene during embryonic development, and that keeps the GNAQ protein getting expressed even after week 9 of development.
As a result, the vascular plexus doesn’t regress like normal, and there ends up being an excess of capillaries in tissues that derive from the ectoderm, specifically those from the cephalic portion of the neural tube, like the brain, eyes, and skin on the face.
Now, the GNAQ mutation occurs sporadically in a random ectodermal cell, which then replicates over and over, so all of the cells that descend from that mutated cell have the mutation.
This means that the earlier the mutation arises in embryological development, the more tissues will be affected, since more tissues will be developing from that mutant cell.
That variation accounts for whether the Sturge-Weber is on one side of the body - unilateral, or both sides - bilateral, and also whether it’s complete, meaning it affects the brain and face, or incomplete, meaning that it affects just one or the other.
So for example, if the mutation occurs very early in development, the syndrome will most likely be bilateral and complete, while if it occurs late in development, the disease will be unilateral and incomplete.
Now, the most common presentation is unilateral and complete disease, so having both the brain and face affected on the same side, and most often the eye is not involved.
In the brain, some individuals develop leptomeningeal angiomas, which are vascular malformations in the meninges which wrap around the brain.
It’s thought that these angiomas lead to pooling of blood, and impaired venous drainage. That makes it harder for fresh arterial blood to flow in, and causes brain ischemia.
Over time, the ischemia causes brain atrophy and the brain tissue can develop areas of calcification. In the skin, the most classic feature is a port-wine stain, which is a purple mark on the face that’s generally present from birth, and in the areas innervated by the trigeminal nerve.
It’s thought that the trigeminal nerve is involved because during embryological development, it’s one of the first cranial nerves to develop from the neural crest cells.
Typically the port wine stain covers the forehead and upper eyelid on one side of the face, but in some it covers the whole face.
In some individuals, there are so many capillaries around the trigeminal nerve that it affects the eye on the same side, causing pooling of blood here as well, with obstruction of venous outflow ultimately leading to high episcleral venous pressure.
Some individuals have congenital trabeculodysgenesis, which is when the trabecular meshwork - which is the part of the eye responsible for draining the aqueous humor from the eye - is underdeveloped.
That leads to glaucoma, which is increased intraocular pressure. Neurologic symptoms of Sturge-Weber syndrome are related to the extent of brain atrophy, and they include things like developmental delay, as well as seizures, and muscle weakness on the side opposite of the port-wine stain, or on both sides if the disease is bilateral.
This is because each side of the body is controlled by the opposite side of the brain. Some individuals develop glaucoma, which can cause reduced vision or even blindness in the affected eye.
Sturge–Weber syndrome is usually suspected when a baby is born with a port-wine stain, and to confirm the diagnosis, brain imaging with a CT or MRI can be done to look for leptomeningeal angiomatosis and the classical type of brain calcifications called tram-track pattern because it literally looks like tramway tracks.
Treatment for Sturge–Weber syndrome is aimed at helping with symptoms, because there’s no cure. Anticonvulsant drugs may be used to control seizures; and if they fail, individuals may get a hemispherectomy, which is where a large portion of the affected part of the brain is removed.
Glaucoma can be managed with some medications like latanoprost, which is a prostaglandin analog that reduces intraocular pressure, and for more serious cases, surgery like a trabeculectomy, which is when a part of the trabecular meshwork is removed to help drainage of aqueous humor.
Finally, for aesthetic reasons, laser treatment can be used to lighten or remove the port-wine stain. All right, as a quick recap, Sturge-Weber syndrome is a neurocutaneous disorder caused by a mutation in the GNAQ gene.
The result is an excess of capillaries in areas of the face innervated by the trigeminal nerve, typically in the forehead and upper eyelid - this is called a port-wine stain.
The eye on the affected side may also develop glaucoma, with increased pressure in the eye, causing reduced vision or even blindness.
Finally, there can be leptomeningeal angiomas on the same side of the port-wine stain that cause brain atrophy and tram-track brain calcification.
Symptoms associated with brain atrophy show on the opposite side of the body, and include seizures and muscle weakness, as well as developmental delay.