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A 1-week-old infant is brought to the clinic for an evaluation of Sturge-Weber syndrome. She was born at 40 weeks' gestation with no complications. Her past personal medical, family medical, and social histories are noncontributory. Physical examination shows vital signs are normal and the patient is resting comfortably. Which of the following findings is most often associated with Sturge-Weber syndrome?
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.
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.