What is the role of genetics in the etiology of Sturge-Weber syndrome (SWS)?

Updated: Dec 26, 2018
  • Author: Masanori Takeoka, MD; Chief Editor: George I Jallo, MD  more...
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The etiology of SWS is primarily likely associated with somatic mosaicism. Huq et al reported evidence of somatic mosaicism in 4 patients with SWS. [26, 27] Tissue samples were via skin biopsy from port-wine stains in 2 patients, and LAs from hemispherectomy in the other 2 patients. Inversion of chromosome arm 4q and trisomy 10 were seen in one patient each. Shirley et al identified a somatic activating c.548G->A mutation in GNAQ (on chromosome 9q21) in samples of affected tissues, in 23 out of 26 study participants with SWS. [28]

Malformed cortical vessels in SWS have been reported to be innervated only by noradrenergic sympathetic nerve fibers, [29] and increased endothelin-1 expression has also been seen in malformed intracranial vessels. These findings may suggest increased vasoconstriction in these abnormal blood vessels, as endothelin-1 is a peptide associated with vasoconstriction.

Fibronectin is a molecule important in regulating angiogenesis, maintenance of the blood-brain barrier, and blood vessel structure and function, as well as brain tissue responses to seizures. Comi et al reported that, in patients with SWS, decreased expression of fibronectin was noted in the leptomeningeal blood vessels, while increased expression was noted in the parenchymal vessels. The leptomeningeal blood vessel circumference was decreased, while blood vessel density was increased in SWS. [30]

Overall, in SWS, an activating somatic mutation in the GNAQ gene (p.Arg183Gln), seen in most cases [28] on chromosome 9 (at 9q21.2), appears to cause alterations in regulation of the structure and function of blood vessels, innervation of the blood vessels, and expression of extracellular matrix and vasoactive molecules.

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