Sturge–Weber syndrome

Sturge-Weber angiomatosis.

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A 20-year-old woman presented with a 1-month history of swollen gums.

Her medical history included seizures for the past 19 years and a macular patch on the right side of her face since birth. She was taking phenytoin for her seizures. Intraoral examination showed extension of the macular patch on the right side of the oral cavity and generalised gingival enlargement.

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On the basis of her history and clinical presentation she was diagnosed with Sturge-Weber angiomatosis and drug-induced gingival enlargement. Extraoral skull radiographs showed tramline calcification because of angiomas affecting the leptomeninges. The patient was given meticulous oral treatment and her antiepileptic medication was changed. The angiomas present in our patient are malformations of blood vessels in the pia mater causing the calcification and loss of nerve cells in the cerebral cortex. These sequelae of the malformations give rise to the clinical symptom of seizures and radiological sign of tramline calcification.

Source: Lancet

 

Sturge–Weber Syndrome and Port-Wine Stains Caused by Somatic Mutation in GNAQ.

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BACKGROUND

The Sturge–Weber syndrome is a sporadic congenital neurocutaneous disorder characterized by a port-wine stain affecting the skin in the distribution of the ophthalmic branch of the trigeminal nerve, abnormal capillary venous vessels in the leptomeninges of the brain and choroid, glaucoma, seizures, stroke, and intellectual disability. It has been hypothesized that somatic mosaic mutations disrupting vascular development cause both the Sturge–Weber syndrome and port-wine stains, and the severity and extent of presentation are determined by the developmental time point at which the mutations occurred. To date, no such mutation has been identified.

METHODS

We performed whole-genome sequencing of DNA from paired samples of visibly affected and normal tissue from 3 persons with the Sturge–Weber syndrome. We tested for the presence of a somatic mosaic mutation in 97 samples from 50 persons with the Sturge–Weber syndrome, a port-wine stain, or neither (controls), using amplicon sequencing and SNaPshot assays, and investigated the effects of the mutation on downstream signaling, using phosphorylation-specific antibodies for relevant effectors and a luciferase reporter assay.

RESULTS

We identified a nonsynonymous single-nucleotide variant (c.548G→A, p.Arg183Gln) in GNAQ in samples of affected tissue from 88% of the participants (23 of 26) with the Sturge–Weber syndrome and from 92% of the participants (12 of 13) with apparently nonsyndromic port-wine stains, but not in any of the samples of affected tissue from 4 participants with an unrelated cerebrovascular malformation or in any of the samples from the 6 controls. The prevalence of the mutant allele in affected tissues ranged from 1.0 to 18.1%. Extracellular signal-regulated kinase activity was modestly increased during transgenic expression of mutant Gαq.

CONCLUSIONS

The Sturge–Weber syndrome and port-wine stains are caused by a somatic activating mutation in GNAQ. This finding confirms a long-standing hypothesis.

 

Source: NEJM