Pathophysiology
Summary
Sturge-Weber syndrome (SWS) is a neurocutaneous disorder characterized by capillary-venous malformations present in the brain, eyes, and skin. The syndrome originates from an activating mutation in the GNAQ gene, which alters the intracellular IP3-DAG pathway. It is not an inherited condition but rather arises due to mosaicism, with the mutation occurring post-fertilization, rendering it a sporadic congenital disease. Clinically, patients often present with a nevus flammeus, commonly referred to as a "port wine stain", predominantly observed in the V1 and V2 trigeminal nerve branches. Furthermore, they may develop leptomeningeal angiomas, which denotes increased vascularity of the pia and arachnoid mater, leading to potential brain compression and seizures. When seizures manifest, they may precipitate acute contralateral hemiparesis. In infants, episcleral hemangiomas may be apparent, predisposing them to early-onset glaucoma and the possible progression to buphthalmos. A significant proportion of affected individuals display intellectual disabilities. On imaging, a characteristic "tram-track" pattern calcification in leptomeningeal angiomas might be discernible.
Tuberous sclerosis complex (TSC) is a neurocutaneous disorder marked by benign hamartomas that localize to various body organs. TSC stems from mutations in either the TSC1 gene on chromosome 9 or the TSC2 gene on chromosome 16, both of which are tumor suppressors. Disruption in these genes impacts the hamartin/tuberin complex, activating the Ras pathway and prompting premature cell cycle activation.
Clinically, patients with TSC present in various ways. CNS signs include glioneuronal hamartomas and subependymal nodules, both of which may precipitate non-communicating hydrocephalus. Early-onset seizures and intellectual disability are also common. Dermatologically, findings include angiofibromas on the face, ash-leaf spots, and shagreen patches, typically found on the lower back. From a cardiovascular perspective, cardiac rhabdomyomas can develop, which can impinge the mitral valve causing mitral regurgitation in infants. Pulmonary manifestations include diffuse interstitial fibrosis and renal angiomyolipomas, the latter of which carry the risk of malignant transformation.
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FAQs
Sturge-Weber syndrome (SWS) is a congenital sporadic neurocutaneous disorder characterized by capillary-venous malformations in the brain, eyes, and skin. It arises from an activating mutation in the GNAQ gene, which occurs post-fertilization, leading to somatic mosaicism, where some cells carry the mutation while others don’t. A hallmark feature of SWS is the nevus flammeus or ‘port wine stain’, caused by abnormal capillary overgrowth in the skin.
SWS presents with leptomeningeal angiomas—vascular malformations of the leptomeninges—typically ipsilateral with a nevus flammeus. These angiomas can cause brain ischemia and pressure necrosis due to vessel compression. Seizures are common in SWS, often linked to acute hemiparesis contralateral to the leptomeningeal angioma. Additionally, infants can present with episcleral hemangiomas in the eye, leading to increased intraocular pressure and early-onset glaucoma. Intellectual disability is also a common presentation.
Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder marked by benign hamartomas in various organs including the brain, eyes, and heart. TSC results from mutations in either the TSC1 or TSC2 genes, both tumor suppressors. These mutations disrupt the hamartin/tuberin complex, leading to unchecked cell cycle activation.
TSC manifests in several ways. CNS signs include glioneuronal hamartomas, primarily in the cerebral cortex, and subependymal nodules lining the ventricular system, which can cause seizures and non-communicating hydrocephalus. Other features include facial angiofibromas, Ash-leaf skin spots, shagreen patches, cardiac rhabdomyomas, and renal angiomyolipomas, which bear a risk of malignant transformation. Intellectual disability is also frequently observed in TSC patients.
Diagnosis of SWS often typically involves imaging studies. X-rays or CT scans can show a ‘tram-track’ pattern, indicating calcification of leptomeningeal angiomas. Clinical signs, such as increased intraocular pressure from episcleral hemangiomas in infants or the presence of a nevus flammeus, further support the diagnosis.
