Continuing Education Activity

Sturge-Weber syndrome is a rare neurocutaneous disorder characterized by a facial port-wine birthmark, leptomeningeal angiomatosis, and ocular involvement, with substantial risk of neurologic, ophthalmologic, and cognitive morbidity. This educational activity reviews the underlying pathophysiology, key neuroimaging findings, and current evidence-based management strategies, including emerging therapies such as inhibition of the mechanistic target of rapamycin and cannabidiol. Emphasis is placed on improving early recognition, accurate diagnosis, and risk stratification to reduce delays in care. Clinicians gain practical skills to optimize seizure control, monitor for glaucoma, and prevent progressive neurologic decline and vision loss. Content also highlights the importance of coordinated care among neurology, ophthalmology, dermatology, and other specialties, demonstrating how effective interprofessional collaboration enhances diagnostic accuracy, supports timely intervention, and improves overall patient outcomes through a structured, team-based approach.

Objectives:

• Identify the key diagnostic criteria for Sturge-Weber syndrome, including the characteristic features of port-wine birthmarks, leptomeningeal angiomatosis, and ocular vascular malformations.
• Interpret brain magnetic resonance imaging findings associated with Sturge-Weber syndrome, including leptomeningeal enhancement, gyriform calcifications, and cortical atrophy, at various stages of disease progression.
• Select evidence-based pharmacologic and surgical treatment strategies for managing seizures, glaucoma, and stroke-like episodes in patients with Sturge-Weber syndrome.
• Collaborate with an interprofessional team, including neurologists, ophthalmologists, dermatologists, geneticists, and nursing staff, to develop coordinated, patient-centered care plans for individuals with Sturge-Weber syndrome.

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Introduction

Sturge-Weber syndrome (SWS), also called encephalotrigeminal angiomatosis, is a rare neurocutaneous syndrome characterized by angiomas involving the face, choroid plexus, and leptomeninges. The facial capillary vascular malformation is also known as a port-wine birthmark and was previously called a port-wine stain or nevus flammeus. This malformation is located in the distribution of the trigeminal nerve.[1]

This condition is the third most common neurocutaneous syndrome after neurofibromatosis and tuberous sclerosis.[2] The neurologic manifestations of SWS include seizures and epilepsy, stroke-like episodes, migraine headaches, hemiparesis, and intellectual disabilities.[3] No curative therapy is currently available; treatment is largely symptomatic and includes anticonvulsants. Recent therapeutic developments aim to stabilize disease progression.[4]

Etiology

SWS is a sporadic developmental disorder caused by somatic mosaic mutations in the GNAQ gene on the long arm of chromosome 9 (9q21).[5][6] The most common mutation in this gene is the R183Q variant in SWS.[7] GNAQ encodes Gαq, which is the α subunit of the heterotrimeric G protein. G proteins are important for signal transduction via G-protein-coupled receptors. The R183Q mutation is the primary mutation identified in the capillaries of port-wine birthmarks with upregulated vascular endothelial growth factor.[8][9]

Evidence suggests that the R183Q mutation results in downstream activation of the Ras/Raf/MEK/ERK (rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase) pathways and hyperactivation of mammalian target of rapamycin activity. These gain-of-function mutations likely cause abnormal capillary proliferation and overgrowth, with endothelial cells activated. Impaired endothelial cell differentiation may also occur, resulting in the dilatation of immature venule-like vessels in the angiomas.[7][10]

Epidemiology

SWS is the third most common neurocutaneous syndrome after neurofibromatosis and tuberous sclerosis, with no known sex-based or racial predilection. The prevalence of Sturge-Weber syndrome is not well known, although the incidence is estimated at 1 in 20,000 to 50,000 live births.[2] Results from a United States (Minnesota) study revealed a prevalence of 0.19 per 100,000 per year.[10] Findings from a Korean registry study showed a prevalence of 3.08 per 100,000 people per year.[2][11]

Pathophysiology

The facial nevus flammeus, or port-wine birthmark, is composed of multiple thin-walled vessels that resemble capillaries. The neuropathological finding is an angioma, consisting of multiple capillaries and small venous channels, usually confined to the pia mater. Associated impairment of superficial venous drainage from the underlying cerebral cortex results in venous stasis and ischemia of the underlying brain parenchyma. These abnormal capillary and venous malformations also exhibit increased permeability, leading to the extravasation of calcium and proteins into the brain parenchyma.

Calcification becomes more prominent over time and is associated with enlarged deep venous drainage, secondary to increased venous pressure. The calcifications are typically seen in the posterior cortical areas and appear gyriform on neuroimaging, classically described as tram-track calcifications. The underlying brain parenchyma becomes atrophic and dyslaminated, with astrogliosis. The brain abnormalities are usually unilateral and ipsilateral to the facial port-wine birthmark. Bilateral brain involvement occurs in about 15% of patients. Results from studies indicate that a bilateral port-wine birthmark is the main risk factor for bilateral brain involvement.[4][12]

History and Physical

Port wine birthmarks (PWB) occur in 3 of every 1000 live births. Only 6% of infants with PWB demonstrated SWS-related neurological involvement. PWB in the ophthalmic (V₁) distribution of the trigeminal nerve carries a risk of 20% to 50% of brain involvement. A high correlation exists between PWB size and the degree of brain involvement.[13] PWB is typically unilateral, present at birth, and does not change with age.[14] This pattern contrasts sharply with that of an infantile hemangioma, which is more common than a PWB but is not present at birth.

PWB grows slowly before involution. If the PWB involves both the upper and lower eyelids, the risk of glaucoma increases by up to 50%. Glaucoma is almost always ipsilateral to the PWB. Not all patients with PWB have SWS. Patients with SWS may present with cerebral symptoms without facial findings. The main neurological manifestations of SWS are as follows:

• Seizures and epilepsy: Seizures represent the most common presenting neurological symptom in SWS, with a median age of onset of 6 months. Approximately 75% of patients present within 1 year of age, and 90% within 2 years after birth. Infantile spasms are seen in approximately 90% of affected patients in the first year of life, followed by atonic, tonic, or myoclonic seizures. Increasing hemiparesis commonly accompanies seizures. Seizures progressively become refractory to medication administration.[15] The seizure focus is typically located in the cerebral cortex beneath the leptomeningeal angiomatosis. Todd paralysis is common and may be a cause of the stroke-like episodes. In addition, seizures may trigger migraine headaches and stroke-like episodes.
• Stroke-like episodes: Stroke-like episodes are transient events of unilateral weakness, usually lasting more than 24 hours; seizures may cause them. Permanent neurological deficits may develop after these transient events. Such episodes may represent Todd paralysis, focal hypoxia, or capillary leakage.
• Migraine headache: Patients with SWS have a much higher prevalence of migraine headaches than the general population, with no sex predilection. The headaches are typically migraine with visual aura.
• Ocular involvement: Glaucoma is very common in SWS. Glaucoma can be either congenital, presenting at birth in 60% of affected patients, or secondary, occurring in late childhood or early adulthood in 40%.[16] Glaucoma occurs in 30% to 70% of patients with SWS when the PWB involves both the upper and lower eyelids. A diffuse choroidal hemangioma is seen in about 20% of patients with SWS and is usually ipsilateral to the facial PWB.[17] Choroidal hemangiomas grow slowly and usually do not cause any symptoms. The retina overlying a choroidal hemangioma may appear normal. However, it may also demonstrate pathological changes such as epithelial atrophy or proliferation, drusen formation, or detachment.
• Cognitive impairment: Learning disabilities, attention deficits, and behavioral issues are common in patients with SWS. These problems are worse when bilateral brain involvement is present or when seizure onset occurs at an earlier age.[18]
• Some endocrine disorders are also more common among patients with SWS and include growth hormone deficiency and hypothyroidism.[19]

Evaluation

According to an interdisciplinary, multicenter consensus, the key diagnostic criteria for SWS require 2 of the following 3 features: a characteristic PWB, a vascular malformation of the eye, and a brain MRI showing leptomeningeal angiomatosis.[20][21] Any neonate at risk for SWS should be referred to an ophthalmologist and a neurologist experienced in caring for patients with SWS. A careful ophthalmologic examination, including intraocular pressure assessment, by an ophthalmologist, is critical for evaluating glaucoma. An experienced neurologist will evaluate the neurological findings and determine the timing and type of MRI needed for the patient's evaluation.

Diagnosis of SWS is based on characteristic clinical symptoms, facial appearance, and MRI findings.[22] Ocular ultrasonography can demonstrate diffuse choroidal thickening, suggesting a choroidal hemangioma. Gyriform calcifications can be seen on skull radiographs and are classically described as the tram-track sign.

Computed tomography is the best modality for detecting calcifications in the brain and also shows other changes, such as cortical atrophy and leptomeningeal enhancement after contrast administration. However, computed tomography uses ionizing radiation, and its routine use in children is not recommended due to ongoing brain development. Consequently, brain MRI with contrast administration is the recommended imaging modality (see Image. MRI Brain Imaging in Sturge-Weber Syndrome).

The most common locations of brain abnormalities in SWS are the occipital, posterior parietal, and temporal lobes. The MRI findings will depend on the stage of the disease. In the early phase, hyperperfusion is transient, with accelerated myelin maturation, leptomeningeal enhancement (serpiginous enhancement along the sulci), and restricted diffusion if an associated acute ischemic event is present.

In the late phase, an increased T2 signal is seen in the region of gliosis with decreased pial enhancement and cortical atrophy. Superficial cortical veins are absent, with prominent deep medullary or subependymal veins and an enlarged choroid plexus. Gyriform calcifications are best seen on T2 or susceptibility-weighted imaging and appear as areas of signal loss along the gyri in a serpentine pattern.

Patients with cutaneous and ocular manifestations and normal brain MRI findings at 1 year of age are unlikely to develop future brain involvement. Choroidal angiomas can be seen on MRI as increased enhancement along the posterior choroid layer of the globe. Fluorodeoxyglucose positron emission tomography may be a useful modality for studying cerebral metabolism in patients with SWS. The affected area is usually hypermetabolic in the early stages, with hypometabolism developing in the late stages.[23] PET may be useful in surgical planning when cortical resection is required for the treatment of intractable seizures.

Treatment / Management

No specific treatment exists for SWS. The primary aim of treating patients with SWS is to decrease seizure activity with anticonvulsant medication. Surgical procedures may be considered in patients who do not respond to medical management and continue to have refractory seizures. The surgical procedures for SWS include hemispherectomy or focal resection of the seizure focus.[4] Patients with bilateral involvement are typically not good candidates for surgery.[24] 

The PWB can be treated with laser photocoagulation, which results in irreversible damage to blood vessels without affecting other skin components. An annual ophthalmologic examination is recommended even if the early evaluation does not detect glaucoma. The goal of glaucoma treatment is to reduce intraocular fluid, thereby lowering intraocular pressure and reducing the potential for visual loss. Topical medication is considered primarily for late-onset glaucoma. Surgical intervention is considered for patients with early-onset glaucoma and associated angle abnormalities and includes goniotomy or trabeculotomy. Further surgical procedures, such as trabeculectomy or a glaucoma drainage device, may be considered for patients with resistant glaucoma.[25] 

Recent Treatment Updates

• Low-dose aspirin: Aspirin is effective in decreasing the frequency of seizures and stroke-like episodes.[26] Aspirin in combination with the anticonvulsant levitiracetam can prevent and delay the onset of both seizures and stroke-like episodes, both presymptomatically and after symptom onset.[27]
• Mammalian target of rapamycin inhibition: Increased activity of the mammalian target of rapamycin (mTOR) is observed in the R183Q GNAQ mutation in SWS. Therefore, patients with SWS could potentially benefit from mTOR inhibition. Oral sirolimus has been shown in many reported cases of SWS to result in improvement in seizures, stroke-like episodes, hypertrophy of pathological tissue, cognitive impairment, and port-wine birthmarks.[6][28][29]
• Cannabidiol, CBD: CBD (brand name Epidiolex) was approved by the United States Food and Drug Administration in 2018 for the treatment of refractory seizures associated with Dravet syndrome and Lennox-Gastaut syndrome. Since then, trials have been performed to assess the efficacy of CBD in other seizure disorders, including SWS. Results from these trials showed improvements in seizure control and other symptoms, including cognitive function, speech and communication, and overall quality of life.[12][13][30]

Differential Diagnosis

The differential diagnosis of SWS includes:

• Blue rubber bleb nevus syndrome
• Klippel-Trenaunay-Weber syndrome
• Posterior fossa abnormalities, hemangiomas, arterial anomalies, cardiac, eye, and sternal anomalies (PHACES) syndrome
• Wyburg-Mason syndrome

SWS can be easily distinguished from these conditions based on clinical history, physical examination, and brain MRI findings.

Prognosis

The prognosis for patients with SWS is guarded and depends on the severity of the associated clinical anomalies.[31] 

Complications

Complications of SWS include:

• Seizures
• Stroke-like episodes
• Glaucoma and other visual problems
• Cognitive impairment
• Endocrine dysfunction

Deterrence and Patient Education

The patient and parents should be educated that there is no cure for this disease and the management is primarily symptomatic treatment to control the neurologic and ocular manifestations.

Pearls and Other Issues

Pearls of SWS include: 

• The most important clinical sign of SWS is the port-wine birthmark. The extent of the birthmark can predict the degree and severity of both brain and eye involvement.
• Brain involvement in SWS determines the severity of disability, including seizures, stroke-like episodes, physical neurological findings, and cognitive impairment.
• A combination of low-dose aspirin and anticonvulsants can delay or diminish the symptoms of SWS, including seizures and stroke-like episodes.
• The mTOR inhibitor sirolimus and CBD are promising novel treatments for patients with SWS.

Enhancing Healthcare Team Outcomes

The treatment of SWS is best accomplished with an interprofessional team approach. The team may include a geneticist, pediatricians, pediatric ophthalmologists, pediatric radiologists, pediatric neurologists, nurse practitioners, and pediatric neurosurgeons. No cure exists for SWS, and all treatments are symptom-based.

In addition to preventing seizures, patients require ophthalmology monitoring due to the risk of developing glaucoma. The skin lesions can be treated by a dermatologist. Nurses play an important role in patient and family education.

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References

1.

Poliner A, Fernandez Faith E, Blieden L, Kelly KM, Metry D. Port-wine Birthmarks: Update on Diagnosis, Risk Assessment for Sturge-Weber Syndrome, and Management. Pediatr Rev. 2022 Sep 01;43(9):507-516. [PubMed: 36045161]

2.

Comi AM. Sturge-Weber syndrome. Handb Clin Neurol. 2015;132:157-68. [PubMed: 26564078]

3.

Dingenen E, Segers D, De Maeseneer H, Van Gysel D. Sturge-Weber syndrome: an update for the pediatrician. World J Pediatr. 2024 May;20(5):435-443. [PubMed: 38658498]

4.

Shah AD, Alexieff P, Tatachar P. Sturge-Weber Syndrome: A Narrative Review of Clinical Presentation and Updates on Management. J Clin Med. 2025 Mar 22;14(7) [PMC free article: PMC11989965] [PubMed: 40217631]

5.

Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, North PE, Marchuk DA, Comi AM, Pevsner J. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med. 2013 May 23;368(21):1971-9. [PMC free article: PMC3749068] [PubMed: 23656586]

6.

Sánchez-Espino LF, Ivars M, Antoñanzas J, Baselga E. Sturge-Weber Syndrome: A Review of Pathophysiology, Genetics, Clinical Features, and Current Management Approache. Appl Clin Genet. 2023;16:63-81. [PMC free article: PMC10145477] [PubMed: 37124240]

7.

Yeom S, Comi AM. Updates on Sturge-Weber Syndrome. Stroke. 2022 Dec;53(12):3769-3779. [PMC free article: PMC11062639] [PubMed: 36263782]

8.

Tan W, Nadora DM, Gao L, Wang G, Mihm MC, Nelson JS. The somatic GNAQ mutation (R183Q) is primarily located within the blood vessels of port wine stains. J Am Acad Dermatol. 2016 Feb;74(2):380-3. [PMC free article: PMC5110233] [PubMed: 26775782]

9.

Gupta SS, Joslyn KE, McKenney KD, Comi AM. Biomarker development in Sturge-Weber syndrome. J Neurodev Disord. 2025 Aug 25;17(1):50. [PMC free article: PMC12376483] [PubMed: 40851064]

10.

Rihani HT, Dalvin LA, Hodge DO, Pulido JS. Incidence of Sturge-Weber syndrome and associated ocular involvement in Olmsted County, Minnesota, United States. Ophthalmic Genet. 2020 Apr;41(2):108-124. [PMC free article: PMC8851558] [PubMed: 32233696]

11.

Ha A, Kim SH, Baek SU, Kim JS, Yoon HJ, Kim YK. Incidence of Sturge-Weber Syndrome and Risk of Secondary Glaucoma: A Nationwide Population-based Study Using a Rare Disease Registry. Am J Ophthalmol. 2023 Mar;247:121-126. [PubMed: 36375589]

12.

Joslyn KE, Truver NF, Comi AM. A Review of Sturge-Weber Syndrome Brain Involvement, Cannabidiol Treatment and Molecular Pathways. Molecules. 2024 Nov 08;29(22) [PMC free article: PMC11596899] [PubMed: 39598668]

13.

Solomon C, Comi A. Sturge-Weber syndrome: updates in translational neurology. Front Neurol. 2024;15:1493873. [PMC free article: PMC11646805] [PubMed: 39687400]

14.

Enjolras O, Riche MC, Merland JJ. Facial port-wine stains and Sturge-Weber syndrome. Pediatrics. 1985 Jul;76(1):48-51. [PubMed: 4011357]

15.

Pinto A, Sahin M, Pearl PL. Epileptogenesis in neurocutaneous disorders with focus in Sturge Weber syndrome. F1000Res. 2016;5 [PMC free article: PMC4805158] [PubMed: 27019697]

16.

Wen T, Wang L, Luo H, Tang L. Sturge-Weber syndrome secondary glaucoma: From Pathogenesis to Treatment. Eye Vis (Lond). 2025 Apr 17;12(1):16. [PMC free article: PMC12004580] [PubMed: 40241121]

17.

Maraña Pérez AI, Ruiz-Falcó Rojas ML, Puertas Martín V, Domínguez Carral J, Carreras Sáez I, Duat Rodríguez A, Sánchez González V. Analysis of Sturge-Weber syndrome: A retrospective study of multiple associated variables. Neurologia. 2017 Jul-Aug;32(6):363-370. [PubMed: 26964511]

18.

Zhang Y, Niu J, Wang J, Cai A, Wang Y, Wei G, Wang H. Neurological function and drug-refractory epilepsy in Sturge-Weber syndrome children: a retrospective analysis. Eur J Pediatr. 2024 Apr;183(4):1881-1890. [PubMed: 38305888]

19.

Hadid SA, Noor L, Baer T, Jacobson RI, Brutsaert E. Hypothalamic-pituitary dysfunction in Sturge-Weber syndrome: case report and review of the literature. J Pediatr Endocrinol Metab. 2024 Jan 29;37(1):80-83. [PubMed: 38006605]

20.

El Hachem M, Diociaiuti A, Galeotti A, Grussu F, Gusson E, Ferretti A, Marras CE, Vecchio D, Cappelletti S, Severino M, Gandolfo C, Reali S, Longo R, D'Amore C, Gariazzo L, Marraffa F, Ciofi Degli Atti ML, Mancardi MM., and the Sturge-Weber Syndrome Multidisciplinary Group. Multidisciplinary, multicenter consensus for the care of patients affected with Sturge-Weber syndrome. Orphanet J Rare Dis. 2025 Jan 16;20(1):28. [PMC free article: PMC11740666] [PubMed: 39819452]

21.

Ramirez EL, Jülich K. Sturge-Weber syndrome: an overview of history, genetics, clinical manifestations, and management. Semin Pediatr Neurol. 2024 Oct;51:101151. [PubMed: 39389653]

22.

Comi AM. Update on Sturge-Weber syndrome: diagnosis, treatment, quantitative measures, and controversies. Lymphat Res Biol. 2007;5(4):257-64. [PubMed: 18370916]

23.

Chugani HT, Mazziotta JC, Phelps ME. Sturge-Weber syndrome: a study of cerebral glucose utilization with positron emission tomography. J Pediatr. 1989 Feb;114(2):244-53. [PubMed: 2783735]

24.

Arzimanoglou AA, Andermann F, Aicardi J, Sainte-Rose C, Beaulieu MA, Villemure JG, Olivier A, Rasmussen T. Sturge-Weber syndrome: indications and results of surgery in 20 patients. Neurology. 2000 Nov 28;55(10):1472-9. [PubMed: 11094100]

25.

Thavikulwat AT, Edward DP, AlDarrab A, Vajaranant TS. Pathophysiology and management of glaucoma associated with phakomatoses. J Neurosci Res. 2019 Jan;97(1):57-69. [PubMed: 29607552]

26.

Bay MJ, Kossoff EH, Lehmann CU, Zabel TA, Comi AM. Survey of aspirin use in Sturge-Weber syndrome. J Child Neurol. 2011 Jun;26(6):692-702. [PubMed: 21427442]

27.

Day AM, Hammill AM, Juhász C, Pinto AL, Roach ES, McCulloch CE, Comi AM., National Institutes of Health Sponsor: Rare Diseases Clinical Research Network (RDCRN) Brain and Vascular Malformation Consortium (BVMC) SWS Investigator Group. Hypothesis: Presymptomatic treatment of Sturge-Weber Syndrome With Aspirin and Antiepileptic Drugs May Delay Seizure Onset. Pediatr Neurol. 2019 Jan;90:8-12. [PMC free article: PMC7288478] [PubMed: 30482419]

28.

Sebold AJ, Day AM, Ewen J, Adamek J, Byars A, Cohen B, Kossoff EH, Mizuno T, Ryan M, Sievers J, Smegal L, Suskauer SJ, Thomas C, Vinks A, Zabel TA, Hammill AM, Comi AM. Sirolimus Treatment in Sturge-Weber Syndrome. Pediatr Neurol. 2021 Feb;115:29-40. [PMC free article: PMC8209677] [PubMed: 33316689]

29.

Sun B, Han T, Wang Y, Gao Q, Cui J, Shen W. Sirolimus as a Potential Treatment for Sturge-Weber Syndrome. 2021 Jan-Feb 01J Craniofac Surg. 32(1):257-260. [PubMed: 32941208]

30.

Smegal LF, Vedmurthy P, Ryan M, Eagen M, Andrejow NW, Sweeney K, Reidy TG, Yeom S, Lin DD, Suskauer SJ, Kalb LG, Salpekar JA, Zabel TA, Comi AM. Cannabidiol Treatment for Neurological, Cognitive, and Psychiatric Symptoms in Sturge-Weber Syndrome. Pediatr Neurol. 2023 Feb;139:24-34. [PubMed: 36508880]

31.

Higueros E, Roe E, Granell E, Baselga E. Sturge-Weber Syndrome: A Review. Actas Dermosifiliogr. 2017 Jun;108(5):407-417. [PubMed: 28126187]

Disclosure: Forshing Lui declares no relevant financial relationships with ineligible companies.

Disclosure: Walter Hall declares no relevant financial relationships with ineligible companies.