Publish date: Posted on
Last updated: April 20, 2022
Keywords #
Sturge-Weber syndrome
port-wine stain
neurocutaneous syndromes
leptomeningeal angioma
Diagnosis #
Sturge-Weber Syndrome (SWS) is a rare, sporadic neurocutaneous disorder characterized by the hallmark triad of a facial port-wine stain, leptomeningeal angiomatosis, and ocular vascular anomalies. Seizures are a common feature of SWS with 75 to 100% of SWS patients eventually developing epilepsy.[1]
SWS is caused by an activating, somatic mutation in the GNAQ gene, located on Chromosome 9. The mutation results in increased signaling of a cell growth pathway that leads to abnormal growth of blood vessels and capillary-venule malformations.[2] The extent of disease depends on the cells affected and the timing at which the mutation occurred during development. Symptoms and their severity are variable. Early recognition and treatment of symptoms are the cornerstone of SWS management.[1]
Key Concepts #
- SWS is characterized by a facial capillary malformation (port-wine stain; usually on the forehead), glaucoma with vascular eye abnormalities, and leptomeningeal angiomas. Other typical features of SWS are visual field defects, seizures, hemiparesis, migraine-like headaches, cognitive deficits, behavioral problems, and stroke-like episodes.[1,2]
- Glaucoma may be congenital, and thus urgent referral to ophthalmology is important.
- Disease symptoms and severity vary from person to person, but typically progress over time.
- The mutation causing SWS is not inherited; it occurs early in embryonic development.
- Presence of a port-wine stain on an infant’s face should spark consideration of SWS – though only a minority of children with facial port-wine stains will have it.
- Imaging may be non-diagnostic initially.[3] Treatment is multifaceted and should be initiated early to avoid disease sequelae.
Epidemiology #
SWS is rare, affecting 1 out of every 20,000 to 50,000 newborns.[1,2] The overall risk of SWS for any kind of facial vascular malformation is ~8%.[1] Port-wine stains occur in 3 of every 1,000 births.[3]
Clinical Features #
Cutaneous Features
- “Port-wine stain” or nevus flammeus which is a capillary or venular malformation located within the dermis, present at birth.
- Usually located on one side of the face (though it can occasionally be bilateral) in the rough distribution of the ophthalmic division of the trigeminal nerve.[1]
- Generally flat initially, pale pink to dark purple in color, may enlarge, raise, and darken over decades.
- The highest risk for ocular and neurological involvement occurs when the port-wine stain involves the trigeminal ophthalmic nerve branch V1 (incidence of involvement 8 to 15%), the upper eyelid, or if it is bilateral and extensive (incidence of involvement 28%).[1]
- Approximately 60% of facial port-wine stains develop associated soft tissue hypertrophy, with bone hypertrophy occurring in 13.8% and progressive ectasia in 48.3%.[2]
- An estimated 13% of SWS cases do not include facial lesions.[4]
- Port-wine stains do not shrink or disappear spontaneously, in contrast to infantile hemangiomas.
Ocular
- Vascular defects of the eyes can include dilated tortuous vessels of the episclera, conjunctiva, choroid, and/or retina.
- Diffuse choroidal hemangioma occurs in 40-50% of patients with SWS. It is typically unilateral and ipsilateral to the facial port-wine stain.[3,4]
- Glaucoma develops in 30-70% of patients, typically ipsilateral to the facial lesion. This is a result of either elevated episcleral venous pressure or anterior chamber abnormalities preventing aqueous humor outflow.[2,3]
- Glaucoma can be congenital, and thus urgent referral to ophthalmology is important.
- Other ocular features include hemangioma-like superficial eyelid changes, buphthalmos (enlargement of the eyeball), and a red-tinted fundus.
Neurologic
- Capillary-venous malformations of the leptomeninges are a hallmark of SWS. The intracranial angiomatosis is usually ipsilateral to the facial lesion.
- Neurologic dysfunction occurs secondary to the effects of the vascular malformation on the brain tissue. Underlying cortical matter may show cortical dysgenesis, calcifications, and atrophy with neuronal cell loss.[2]
- Vascular steal phenomena may develop around the angiomas, resulting in cortical hypoxia and ischemia.
- Seizures are a common feature in SWS, occurring in 70 to 90% of patients. Of these, 75% manifest in the first year of life.[2]
- Severe or treatment-refractory seizures are associated with increased likelihood of developmental and intellectual disabilities.
- Other neurologic symptoms include slowly-progressive hemiparesis (occurring in 25-60% of SWS), migraine-like headaches, stroke-like episodes, and visual field defects.
- Neuropsychological developmental delays, especially learning disabilities and ADHD, are common in SWS.
Other
- Endocrine disorders due to hypothalamic-pituitary dysfunction, including growth hormone deficiency and hypothyroidism, have been described in SWS.[1]
Differential Diagnoses #
- Nevus simplex (“salmon patch”) Port-wine stains typically have a more lateralized location, are more intense in color, and have sharply demarcated borders. Nevus simplex are generally less demarcated, pale pink to rose colored, and are more centrally located. They can be difficult to differentiate.[2]
- Infantile Hemangioma
- Megalencephaly-capillary-malformation-polymicrogyria syndrome
- Beckwith-Wiedemann syndrome facial port-wine stain, macroglossia, omphalocele, visceral hyperplasia
The main diagnostic goal is to identify children with isolated port-wine stains from those with underlying brain and eye involvement and thus likely SWS.[3]
Diagnostic Workup #
SWS should be suspected in any patient with a port-wine stain involving the forehead or upper eyelid.[2] Diagnosis is based on presentation and imaging. Brain MRI, specifically T1-weighted with gadolinium enhancement, is the diagnostic test of choice.[1] Characteristic findings include areas of leptomeningeal thickening with increased contrast uptake, venular enlargement and dilation of transmedullary/periventricular veins, and enlargement of the choroid plexus.[3] However, leptomeningeal angiomas may be undetectable before age 3 months; thus, diagnostic MRI is recommended once the patient has reached 3-6 months of age.[2]
Other imaging studies include the following: head CT may reveal enlarged choroid plexus and ventricles with reduced parenchymal volume; occasionally early calcifications may be present. Head CT is often the first imaging test used in patients presenting to the ER with seizures or stroke-like events. Plain X-ray of the head may reveal the classic gyriform calcifications of the cortex in a “rail-road track” pattern, though this is typically a later finding in children older than 2 years. Angiography does not show the angioma, but reveals a lack of superficial cortical veins, along with non–filling dural sinuses and abnormal, tortuous cerebral veins.[1,2,4]
EEG is used for the evaluation of seizures. EEG is asymmetric in SWS patients with abnormalities on the affected brain hemisphere, such as background slowing, reduced voltages, and epileptiform activity. [1]
Ophthalmologic examination is indicated in infants with SWS involving the eyelid or forehead, and should be repeated every 3 months for the first year of life. All patients with SWS should continue to have eye exams annually.
Treatment #
Pulsed dye laser is the treatment of choice for facial port-wine stains, though complete clearance is rare.[5] The lesions may darken and/or become nodular if left untreated.[6]
Management of seizures and/or epilepsy with early and aggressive treatment is critical to prevent progression of neurologic damage. Carbamazepine and oxcarbazepine have been shown to have the best seizure control in SWS.[7] Surgery may be indicated in cases of treatment-refractory epilepsy. It is important to note that fevers and infections can trigger seizures.
Acetylsalicylic acid (aspirin) at anti-platelet doses reduces the frequency and severity of vascular ischemia in SWS patients.[2] Glaucoma treatment with eye drops is preferable to reduce intraocular pressures; although surgery may be necessary (trabeculectomy, goniotomy).
Physical and/or occupational therapy is recommended for patients with hemiparesis or other neurologic sequelae. Stimulant medications, behavioral psychology, and specialized education programs are recommended for patients with cognitive deficits and/or ADHD.
References #
- Sudarsanam A, Ardern-Holmes SL. Sturge-Weber syndrome: from the past to the present. Eur J Paediatr Neurol. 2014;18(3):257-266.
- Higueros E, Roe E, Granell E, Baselga E. Sturge-Weber Syndrome: A Review. Actas Dermosifiliogr. 2017;108(5):407-417.
- Comi AM. Update on Sturge-Weber syndrome: diagnosis, treatment, quantitative measures, and controversies. Lymphat Res Biol. 2007;5(4):257-264.
- Takeoka M. Sturge-Weber syndrome. Medscape. 2018. Published December 26, 2018. Accessed September 23, 2019.
- van Raath MI, Chohan S, Wolkerstorfer A, van der Horst C, Storm G, Heger M. Port wine stain treatment outcomes have not improved over the past three decades. J Eur Acad Dermatol Venereol. 2019;33(7):1369-1377.
- Updyke KM, Khachemoune A. Port-Wine Stains: A Focused Review on Their Management. J Drugs Dermatol. 2017;16(11):1145-1151.
- Kaplan EH, Kossoff EH, Bachur CD, et al. Anticonvulsant Efficacy in Sturge-Weber Syndrome. Pediatr Neurol. 2016;58:31-36.
