Sturge-Weber Research Articles

Phenotypic Spectrum of GNA11 R183C Mosaicism.

Many vascular anomalies harbor postzygotic somatic variants in GNAQ and GNA11; however, the phenotype of specific G-protein variants has not been well described. We report the clinical characteristics of 17 patients with a GNA11 R183C variant. This case series is derived from a multinational cohort of vascular anomaly patients whose pathogenic mutations were identified using high-depth next generation sequencing. Data include vascular anomaly features, imaging reports, and extracutaneous manifestations of the GNA11 R183C variant. We identified 17 subjects (median age 18 years [range 6-67]) with somatic GNA11 R183C variant. All patients had vascular lesions of the skin that presented as pink-to-red in children and deeper red in adults. Most lesions were large, poorly demarcated, and reticulated patches that were often bilaterally distributed. Nevus anemicus was observed in 53% (N = 9) and dermal melanocytosis in 13.3% (N = 2) of individuals. 82% (N = 14) of patients had limb growth discrepancies, and 1 patient had marked thoracic hypoplasia. 47% (N = 8) of patients had facial involvement, and 41% (N = 7) had forehead involvement. One patient experienced seizures due to right hemispheric leptomeningeal angiomatosis consistent with Sturge-Weber syndrome. Other findings included glaucoma (29%, N = 5) and psychomotor delay (29%, N = 5). These findings contribute to our understanding of the clinical spectrum of GNA11 R183C capillary malformations(CMs); patients characteristically present with extensive, bilateral, poorly demarcated, pink-to-red CMs associated withnevus anemicus. Glaucoma and growth discrepancies (overgrowth or undergrowth) are common. Leptomeningeal angiomatosis and developmental delay can occur, appearing potentially less prevalent and severe than GNAQ-associated disease.

Sturge–Weber syndrome: updates in translational neurology

Sturge–Weber syndrome (SWS) is a rare congenital neurovascular disorder that initially presents with a facial port-wine birthmark (PWB) and most commonly associated with a R183Q somatic mosaic mutation in the gene GNAQ. This mutation is enriched in endothelial cells. Contrast-enhanced magnetic resonance imaging (MRI) diagnoses brain abnormalities including leptomeningeal vascular malformation, an enlarged choroid plexus, and abnormal cortical and subcortical blood vessels. Mouse SWS models identify dysregulated proteins important for abnormal vasculogenesis and blood brain barrier permeability. Recent clinical research has focused on early diagnosis, biomarker development, presymptomatic treatment, and development of novel treatment strategies. Prospective pilot clinical drug trials with cannabidiol (Epidiolex) or with sirolimus, an mTOR inhibitor, indicate possible reductions in seizure frequency and improved cognitive outcome. This review connects the most recent molecular research in SWS cell culture and animal models to developing new treatment methods and identifies future areas of research.

Paternal, Maternal, and Familial Factors as Predictors of Sturge–Weber Syndrome Neurological Outcome

Objectives: To identify potential risk factors influencing Sturge–Weber Syndrome (SWS) and neurological outcomes in individuals with SWS and port-wine birthmarks from paternal, maternal, and familial factors. Methods: This study follows a retrospective cross-sectional design. Clinical visits took place at the Kennedy Krieger Institute, a tertiary care center. Participants were individuals with SWS or port-wine birthmarks. Results: Higher paternal age at conception was associated with a range of cognitive dysfunctions in offspring with SWS brain involvement. Indeed, paternal age was associated with low intelligence quotient (n = 25, P = .004), strokes or stroke-like episodes (n = 34, P = .030), gross and/or fine motor delay (n = 34, P = .036), delays in ability to perform activities of daily living (n = 30, P = .012), and delayed learning compared to peers (n = 31, P = .027). Furthermore, paternal age was correlated with worse cognitive outcomes, as measured by cognitive Neuroscore (r s = 0.575, P < .001, n = 32). When maternal thyroid disease and hypertension were present during pregnancy, offspring were more likely to experience low intelligence quotient (n = 30, P = .041) and regression of any abilities (n = 37, P = .045), respectively. Logistic regression confirmed the association between paternal age and severe cognitive Neuroscore (β = .580, P = .033, odds ratio: 1.79, 95% confidence interval: 1.05–3.04), even when controlling for the effects of seizures and strokes or stroke-like episodes. Conclusions: Prenatal factors were associated with neurological symptoms in subjects with SWS. Older paternal age, in particular, may predict worse neurocognitive outcomes. Further research is needed in larger cohorts to determine the value of the identified prenatal factors as prognostic tools. Likewise, animal models may be used to determine the impact of prenatal factors on the severity of outcome.

R183Q GNAQ Sturge–Weber Syndrome Leptomeningeal and Cerebrovascular Developmental Mouse Model

Objective(s): Sturge–Weber syndrome (SWS), a rare neurovascular malformation disorder, is usually caused by the R183Q GNAQ somatic mosaic mutation enriched in brain endothelial cells. A developmental mouse model of SWS brain involvement is needed to investigate mutation impact upon brain vascular development and to facilitate preclinical drug studies. Methods: A new Tet-ON R183Q GNAQ transgenic mouse line was paired with rtTA tet transactivator mice under the Tie2 promoter to generate mice expressing endothelial R183Q GNAQ in the presence of doxycycline. Litters were perfused at P14-17; half received a subseizure dose (1.5 mg/kg; intraperitoneal) of kainate an hour before perfusion. A subset was perfused with Evans blue. Fixed mouse brains were stained with X-gal, DAPI, and antibodies for Gαq, Tie2, phosphorylated-S6, and claudin-5. Images were scored for vessel staining intensity. Results: X-gal staining was seen only in mutant mice; leptomeningeal endothelial X-gal staining was more frequent in kainate-treated mice (P < 0.001). When perfused with Evans blue, only mutant brains showed severe staining (P = 0.028). Median phosphorylated-S6 vessel scores were significantly higher in the leptomeninges of mutant mice (P = 0.035). Mutant cortical microvessels demonstrated discontinuous claudin-5 and phosphorylated-S6 staining as well as increased vessel length in kainate-treated mice (P = 0.024). Conclusions: The new R183Q GNAQ Tet-ON developmental mouse brain model of SWS demonstrates endothelial expression of mutant Gαq associated with blood–brain barrier breakdown, altered vascular mammalian target of rapamycin activity, and abnormal cortical microvessel structure. This new translational model can be used to develop new drug targets and treatments for SWS.

A Review of Sturge-Weber Syndrome Brain Involvement, Cannabidiol Treatment and Molecular Pathways.

Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder typically caused by a somatic mosaic mutation in R183Q GNAQ. At-risk children present at birth with a capillary malformation port-wine birthmark. The primary diagnostic characteristic of the disorder includes leptomeningeal enhancement of the brain, which demonstrates abnormal blood vessels and results in impaired venous drainage and impaired local cerebral perfusion. Impaired cerebral blood flow is complicated by seizures resulting in strokes, hemiparesis and visual field deficits, hormonal deficiencies, behavioral impairments, and intellectual disability. Therefore, anti-seizure medication in combination with low-dose aspirin is a common therapeutic treatment strategy. Recently published data indicate that the underlying mutation in endothelial cells results in the hyperactivation of downstream pathways and impairment of the blood-brain barrier. Cannabidiol (CBD) has been used to treat medically refractory seizures in SWS due to its anti-seizure, anti-inflammatory, and neuroprotective properties. Pilot research suggests that CBD improves cognitive impairment, emotional regulation, and quality of life in patients with SWS. Recent preclinical studies also suggest overlapping molecular pathways in SWS and in CBD, suggesting that CBD may be uniquely effective for SWS brain involvement. This review aims to summarize early data on CBD's efficacy for preventing and treating epilepsy and neuro-cognitive impairments in patients with SWS, likely molecular pathways impacted, and provide insights for future translational research to improve clinical treatment for patients with SWS.

Circumscribed choroidal hemangioma in Sturge-Weber syndrome

We report on a19-year-old patient with Sturge-Weber syndrome (SWS), accompanied by aNaevus flammeus, secondary glaucoma, and glaucomatous optic atrophy of the right eye. The painful and blind eye was enucleated. Histopathological analysis revealed acircumscribed choroidal hemangioma around the optic nerve and asmaller extrascleral hemangioma. Molecular genetic testing excluded GNA11, GNAQ, or GNAS mutations. Our work illuminates the clinical, histological, and molecular genetic aspects of this rare case, contributing to the differential diagnosis of ocular conditions in patients with SWS.

Distribution of Port-Wine Birthmarks and Glaucoma Outcomes in Sturge-Weber Syndrome

PurposeTo identify which features of Sturge-Weber Syndrome (SWS) were most associated with glaucoma onset, severity, and treatment failure at a tertiary care center. DesignRetrospective cross-sectional study. SubjectsChildren who had SWS with and without glaucoma. MethodsElectronic health records were reviewed for all children with SWS presenting between 2014-2020. Examination and imaging findings from dermatology, neurology, and ophthalmology were collected. Logistic regression was used to identify factors associated with glaucoma-related outcomes. Main Outcome MeasuresPrimary outcomes included glaucoma development, progression to surgery, and treatment failure. Failure was defined as having a final intraocular pressure >21 mmHg, devastating complication, or ≤20/200 vision. ResultsTwenty-three of 44 SWS patients (52.3%) developed glaucoma, and 6 of 23 patients (26.1%) had both eyes affected. Sixteen of 29 eyes (55.2%) required surgery, and 29.6% overall met our failure criteria (mean follow-up: 5.1±4.3 years). Glaucoma diagnosis was associated with bilateral port wine birthmarks (PWB; OR 5.9; 95% CI 1.3-43.2), PWB with any lower eyelid involvement (OR 9.7, 95% CI 2.6-44.5), and choroidal hemangiomas (OR 3.8, 95% CI 1.1-13.8), but was not associated with upper eyelid or leptomeningeal angiomas, seizures, prior hemispherectomy or pulsed-dye laser. Eyes that progressed to surgery were more likely to have PWB affecting the lower eyelid (OR 33.7, 95% CI 4.5-728.0). No clinical or demographic factors were associated with treatment failure. In most cases, angle surgery failed (72.7%) but was a temporizing measure before subconjunctival filtering surgery. ConclusionsLower eyelid and choroidal angiomas were associated with glaucoma diagnosis, suggesting a spatial relationship with SWS findings. However, leptomeningeal angiomas were not associated possibly because these are further from the eye.

AESTHETIC SURGICAL APPROACH FOR STURGE-WEBER SYNDROME AND FACIAL ARTERIOVENOUS TUMORS

Introduction: Sturge-Weber Syndrome (SWS) is a rare, congenital neurovascular condition associated with facial cutaneous capillary or venous malformations. The manifestations are intrinsically related to vascular malformations, resulting in neurological symptoms, soft tissue abnormalities, and restricted bone growth. Methodology: This is a case report of a single patient diagnosed with SWS, following the guidelines established by Resolution 466/12 of the National Health Council of Brazil (CNS). Results and Discussion: A Vascular Surgery approach with embolization was performed prior to the Plastic Surgery intervention. It is important to note that this particular patient did not present the common neurological manifestations. Additionally, port-wine stains manifested as giant hemangiomas on the face. Conclusion: A multidisciplinary team is essential for patients with this condition, as it can facilitate surgical resection when vascular studies are performed prior to surgery. Moreover, a multidisciplinary approach is crucial due to the varied clinical presentation and chronic conditions that require treatment.

Tackling the tubes of refractory Sturge–Weber syndrome with secondary glaucoma: A surgeon’s nightmare!

Hypotony with shallow anterior chamber (AC) post glaucoma surgery in Sturge–Weber syndrome (SWS) patients is commonly due to choroidal effusions. We report two cases of SWS patients having hypotony and shallow AC after Ahmed Glaucoma valve (AGV) implantation with no wound leak or choroidal effusion. Case 1 had persistent shallow AC, which was diagnosis of exclusion, as valve malfunction, a rare occurrence in AGV. Case 2 resolved after AC reformation with 1.8% sodium hyaluronate. Two cases describe the clinical approach and surgical management in patients of hypotony with shallow AC after AGV implantation in SWS patients.

Intracerebral hemorrhage in Sturge Weber Syndrome: A case report

Background. Encephalotrigeminal angiomatosis also called Sturge Weber Syndrome (SWS) is neurocutaneous abnormality with angioma affecting the leptomeninges and the face skin, commonly in the eyes and maxillary distribution of trigeminal nerve. The characteristic of SWS is dilated face skin veins, and referred to nevus flammeus and port wine stain. Case reports. We report a case of Sturge Weber Syndrome in a 41 years old male with uncontrolled hypertension and smoking, left-sided weakness, and left-sided facial port wine stain. Conclusions. Neurological examination was suggestive of SWS and further radiological examination confirmed the diagnosis.

Sturge weber syndrome: A case report.

This report presents a 14-year-old male with seizures and facial port-wine stains, who upon further evaluation was found to have SWS. Early diagnosis and consistent treatment of Sturge-Weber syndrome in children are essential to prevent seizures and improve quality of life. Anti-seizure medications play a crucial role in preventing and controlling seizures.

Similarities and differences between brain and skin GNAQ p.R183Q driven capillary malformations.

Capillary malformations (CM) are congenital vascular irregularities of capillary and venous blood vessels that appear in the skin, leptomeninges of the brain, and the choroid of the eye in the disorder known as Sturge Weber Syndrome (SWS). More common are non-syndromic CM found only in the skin, without brain or ocular involvement. A somatic activating mutation in GNAQ (p.R183Q) is found in ~ 90% of syndromic and non-syndromic CM specimens and is present in CD31pos endothelial cells isolated from brain and skin CM specimens. Endothelial expression of the GNAQ p.R183Q variant is sufficient to form CM-like vessels in mice. Given the distinct features and functions of blood vessels in the brain versus the skin, we examined the features of CM vessels in both tissues to gain insights into the pathogenesis of CM. Herein, we present morphologic characteristics of CM observed in specimens from brain and skin. The GNAQ p.R183Q variant allelic frequency in each specimen was determined by droplet digital PCR. Sections were stained for endothelial cells, tight junctions, mural cells, and macrophages to assess the endothelium as well as perivascular constituents. CM blood vessels in brain and skin were enlarged, exhibited fibrin leakage and reduced zona occludin-1 and claudin-5, and were surrounded by MRC1pos/LYVE1pos macrophages. In contrast, the CMs from brain and skin differ in endothelial sprouting activity and localization of mural cells. These characteristics might be helpful in the development of targeted and/or tissue specific therapies to prevent or reverse non-syndromic and syndromic CM.

Sturge-Weber Syndrome: a case report

Sturge-Weber syndrome is a rare congenital, non-familial sporadic condition also known as encephalotrigeminal angiomatosis, is a phakomatoses consisting of neurological, skin and ocular manifestations. Symptoms reported varies in severity and age of onset but it is commonly detected in infancy. The Ophthalmic feature of this disease consists of glaucoma and is also associated with vascular manifestation of the conjunctiva, epi-sclera, choroid and retina. In the present case, a 19-year-old male presented with a port wine stain on the right side of the face, leptomeningeal angioma, ocular hypertension, temporal hemianopia of the left eye and choroidal hemangioma with macular scar of the right eye, seizure and weakness of the left side of the body. The purpose of presenting the case is to illustrate both the characteristic presentation and to underline the importance of its diagnosis in the clinical ophthalmological practice. BIRDEM Med J 2024; 14(3): 166-169

Enhancing neurosurgical interventions for Sturge-Weber syndrome with AI technologies

Enhancing neurosurgical interventions for Sturge-Weber syndrome with AI technologies

Vascular Anomalies and Congenital Infiltrating Lipomatosis May Affect Dental Maturation and Development - a Case Control Study.

Vascular anomalies are often associated with hypertrophy and asymmetry of soft tissues and bony structures. The aim of this retrospective cross-sectional radiographic study was to evaluate dental maturation and development in patients with facial vascular anomalies and congenital infiltrating lipomatosis. A sample of 342 patients with different vascular anomalies or congenital infiltrating lipomatosis involving the head and neck area was narrowed down to 31 patients with dental panoramic radiographs taken in the mixed dentition. A control group of 172 age-matched healthy subjects was used. Individual permanent teeth were given a maturation score from 1 to 12 and alveolar eruption stage according to Haavikko et al. 1970. The laterality of the anomaly was noted if applicable. Differences in dental development between affected and unaffected sides were recorded. The study data included both syndromic and non-syndromic vascular anomalies as well as congenital infiltrating lipomatosis and segmental odontomaxillary dysplasia. Teeth on the side of the anomaly were more developed and the eruption of teeth was accelerated with canines, premolars and second molars being most affected. Interestingly all the patients with Sturge-Weber syndrome (n = 4) and infiltrating lipomatosis (n = 2) showed accelerated dental maturation of multiple permanent teeth on the side of the anomaly. Hypodontia, dental root resorption and macrodontia were also found. Accelerated development and eruption of permanent teeth unilaterally in patients with vascular anomalies and congenital infiltrating lipomatosis may have a significant impact on the developing occlusion and should be thus followed by an orthodontist.

Assessment of the Corneal Biomechanical Features of Sturge-Weber Syndrome Using Dynamic Ultrahigh-speed Scheimpflug Imaging.

To evaluate the corneal biomechanical characteristics of eyes with Sturge-Weber syndrome (SWS) secondary glaucoma (SSG) by analyzing corneal biomechanical parameters obtained using the Corneal Visualization Scheimpflug Technology instrument (Corvis ST). In patients with SWS, eyes affected by SSG were designated as the SSG group while the contralateral eyes were designated as the SWS contralateral group (SC group). Patients from the myopia clinic served as the control group. Dynamic corneal response parameters (DCRs) including the stress-strain index (SSI)-a critical material stiffness parameter that excludes interference from IOP and central corneal thickness (CCT)-were analyzed. For CCT, no significant difference was observed between the SSG and SC groups. However, significant differences were found between the SSG and control groups and between the SC and control groups. Parameters such as HC Time, A1 Deformation Amp., A2 Deformation Amp., length of Whole Eye Movement (WEM), DA Ratio Max (2 mm), PachySlope, DA Ratio Max (1 mm), and ARTh showed significant differences between the SSG group and control group. In the SSG group, 4 of night eyes had an SSI of less than 0.85. Some DCRs indicated a stiffer cornea in the SSG group, possibly due to a thicker cornea in this group. On analyzing SSI, it was found that corneal material properties change, becoming less stiff in some of the patients with SSG. In conclusion, our study provides a preliminary exploration of the biomechanical properties of SWS secondary glaucoma.

54402 Investigating a Possible Association of Hearing Impairment with Port-Wine Stains and Sturge-Weber Syndrome

54402 Investigating a Possible Association of Hearing Impairment with Port-Wine Stains and Sturge-Weber Syndrome

Feasibility and Potential Diagnostic Value of Noncontrast Brain MRI in Nonsedated Children With Sturge-Weber Syndrome and Healthy Siblings.

Postcontrast magnetic resonance imaging (MRI), obtained under anesthesia, is often used to evaluate brain parenchymal and vascular abnormalities in young children, including those with Sturge-Weber syndrome. However, anesthesia and contrast administration may carry risks. We explored the feasibility and potential diagnostic value of a noncontrast, nonsedate MRI acquisition in Sturge-Weber syndrome children and their siblings with a wide range of cognitive and behavioral functioning. Twenty children (10 with Sturge-Weber syndrome and 10 healthy siblings; age: 0.7-13.5 years) underwent nonsedate 3-tesla (T) brain MRI acquisition with noncontrast sequences (including susceptibility-weighted imaging) prospectively along with neuropsychology assessment. All images were evaluated for quality, and MRI abnormalities identified in the Sturge-Weber syndrome group were compared to those identified on previous clinical pre- and postcontrast MRI. Nineteen participants (95%) completed the MRI with good (n = 18) or adequate (n = 1) quality, including all children with Sturge-Weber syndrome and all 5 children ≤5 years of age. The Sturge-Weber syndrome group had lower cognitive functions than the controls, and both groups had several children with behavioral issues, without an apparent effect on the success and quality of the MR images. Susceptibility-weighted imaging detected key venous vascular abnormalities and calcifications and, along with the other noncontrast sequences, provided diagnostic information comparable to previous clinical MRI performed with contrast administration under anesthesia. This study demonstrates the feasibility and the potential diagnostic value of a nonsedate, noncontrast MRI acquisition protocol in young children including those with cognitive impairment and/or behavioral concerns. This approach can facilitate clinical trials in children where safe serial MRI is warranted.

Alternative Venous Pathways: A Potential Key Imaging Feature for Early Diagnosis of Sturge-Weber Syndrome Type 1.

Sturge-Weber syndrome is a rare congenital disorder characterized by cortical atrophy and calcifications on late-stage imaging. Understanding the evolution of brain lesions is crucial for effective early interventions, yet the timeline remains unclear. We aimed to evaluate early brain MRI findings and their progression longitudinally on follow up MRI in children diagnosed with Sturge-Weber syndrome. We retrospectively included all children with a confirmed diagnosis of Sturge-Weber syndrome between 2009 and 2023 that had at least 2 available MRIs performed before the age of 2 years. A pediatric radiologist and a pediatric neuroradiologist evaluated all the MRI scans for pial enhancement, choroid plexus enlargement, atrophy, calcifications, a prominent subarachnoid varicose network, trans medullary veins, subependymal veins, and deep extra ventricular veins. Descriptive analysis was used for demographic data and brain lesion prevalence. Cumulative incidence curves were used to show the timeline of emerging lesions. K-means clustering was used to categorize the lesions based on their prevalence at 1, 2, 3, 6, 12, 18, and 24 months after birth. Nine patients met the inclusion criteria. Median ages at the first and last MRIs were 35 days (IQR: 11-123) and 294 days (IQR: 208-465), respectively. The most prevalent lesions at the first MRI were subarachnoid varicose network (88.9%) and trans medullary veins (77.8%), while prevalence of atrophy and calcifications differed most between the first and last MRIs. The results of the elbow method and K-means clustering showed that we can divide Sturge-Weber syndrome lesions into 3 groups based on their timeline of emergence. The first cluster contained subarachnoid varicose network, trans medullary veins, subependymal veins, and choroid plexus enlargement. The second cluster contained deep extra ventricular veins, pial enhancement, accelerated myelination, and atrophy. The last cluster contained calcifications. Our findings suggest that dilated venous channels emerge early as a compensatory mechanism, preceding atrophy and calcification. Additionally, these dilated channels precede the appearance of abnormal contrast enhancement of the pia, often termed leptomeningeal angioma. This underscores the importance of early recognition and monitoring of these initial imaging indicators in clinical practice. ASL = Arterial Spin Labelled; MinIP = Minimum intensity projection; SWS = Sturge-Weber Syndrome.

Under Pressure: A Case of Developmental Glaucoma and Congenital Glaucoma in Sturge–Weber Syndrome

Abstract Sturge–Weber syndrome (SWS), also known as encephalo-trigeminal angiomatosis, is a sporadic, congenital neurocutaneous disorder. It is characterized by capillary malformation affecting the brain, meninges, eyes, and skin. The ophthalmic, maxillary, and mandibular distributions of the trigeminal nerve are involved. Eye involvement with vascular malformation produces glaucoma and can lead to vision loss. Here, we present a rare case of SWS with port-wine stain, painful vision loss in left eye, and open-angle glaucoma in the other eye of the same patient. The painful blind eye was treated with cyclocryotherapy with successful control of intraocular pressure.