GNAQ mutations drive port wine birthmark-associated Sturge-Weber syndrome: A review of pathobiology, therapies, and current models

Abstract

Port-wine birthmarks (PWBs) are caused by somatic, mosaic mutations in the G protein guanine nucleotide binding protein alpha subunit q (GNAQ) and are characterized by the formation of dilated, dysfunctional blood vessels in the dermis, eyes, and/or brain. Cutaneous PWBs can be treated by current dermatologic therapy, like laser intervention, to lighten the lesions and diminish nodules that occur in the lesion. Involvement of the eyes and/or brain can result in serious complications and this variation is termed Sturge-Weber syndrome (SWS). Some of the biggest hurdles preventing development of new therapeutics are unanswered questions regarding disease biology and lack of models for drug screening. In this review, we discuss the current understanding of GNAQ signaling, the standard of care for patients, overlap with other GNAQ-associated or phenotypically similar diseases, as well as deficiencies in current in vivo and in vitro vascular malformation models.

Concurrent Occurrence of Port-Wine Stain and Glaucoma in Sturge-Weber Syndrome: A Case Report

“…PWS is a birthmark that appears as a reddish or purplish discolouration of the skin [ 2 ]. It is caused by an abnormal buildup of blood vessels in the affected area, and is typically present at birth.…”

“…It is caused by an abnormal buildup of blood vessels in the affected area, and is typically present at birth. PWS can occur anywhere in the body, but most commonly appears on the face, head, and trunk [ 2 ]. Treatment for PWS typically involves laser therapy, which uses intense light to shrink the blood vessels and improve the appearance of the birthmark [ 2 ].…”

“…PWS can occur anywhere in the body, but most commonly appears on the face, head, and trunk [ 2 ]. Treatment for PWS typically involves laser therapy, which uses intense light to shrink the blood vessels and improve the appearance of the birthmark [ 2 ]. The success of treatment depends on the size, location, and depth of the stain, and may require multiple treatments over time (Figure 7 ) [ 2 ].…”

“…These purplish lesions were evocative of port-wine stains (nevus flammeus) involving the back of the neck and shoulder that did not cross the midline (Figure 2 ). Nevus flammeus or port-wine stain is a benign congenital capillary malformation usually presenting as a unilateral pink, purplish or bright red patch anywhere on the body [ 2 ].…”

Sturge-Weber Syndrome: A Review of Pathophysiology, Genetics, Clinical Features, and Current Management Approache

“…A similar strategy, as used for the prevention of status epilepticus in Dravet syndrome, may be considered. 111 Low-dose aspirin (3-5 mg/kg/day) can be used as concomitant therapy (in addition to antiepileptic drugs), as it decreases both the frequency and severity of headaches, seizures, and stroke-like events in patients with SWS. 50 Aspirin was demonstrated to be safe and well tolerated in a pediatric cohort study.…”