- John B Bodensteiner, MD
John B Bodensteiner, MD
- Senior Associate Consultant in Child and Adolescent Neurology
- Mayo Clinic College of Medicine
- Section Editors
- Marc C Patterson, MD, FRACP
Marc C Patterson, MD, FRACP
- Section Editor — Pediatric Neurology
- Professor of Neurology, Pediatrics, and Medical Genetics
- Chair, Division of Child and Adolescent Neurology
- Mayo Clinic College of Medicine
- Moise L Levy, MD
Moise L Levy, MD
- Section Editor — Pediatric Dermatology
- Professor of Pediatrics and Medicine (Dermatology)
- Dell Medical School, University of Texas, Austin
- Clinical Professor of Dermatology and Pediatrics
- Baylor College of Medicine
Sturge-Weber syndrome (SWS) is a rare congenital vascular disorder characterized by facial capillary malformation (port wine stain) and associated capillary-venous malformations affecting the brain and eye. It is not a heritable disorder. Thus, recurrence is unlikely.
GENETICS AND PATHOGENESIS
The cause of SWS is somatic mosaic mutations in the GNAQ gene, as identified in a study that performed whole-genome sequencing of affected and normal tissue samples from three patients with SWS . This process identified a GNAQ single-nucleotide variant (c.548G→A, p.Arg183Gln) shared by affected tissue from all three patients. The mutation was also found in samples of affected tissue from 23 of 26 subjects (88 percent) with SWS and 12 of 13 subjects (92 percent) with nonsyndromic (isolated) port wine stains, but in none of 4 subjects with other cerebrovascular malformations and in none of 6 control subjects. The prevalence of the mutation in affected tissues ranged from 1 to 18 percent. These findings confirm the longstanding hypothesis that the capillary-venous malformations of SWS, historically called angiomata, result from somatic mutations in fetal ectodermal tissues that cause inappropriate control or maturation of capillary blood vessel formation [2,3].
The GNAQ gene encodes a guanine nucleotide binding protein, G-alpha-q, that functions to regulate intracellular signaling pathways. The p.Arg183Gln somatic GNAQ mutation activates a set of signalling pathways that are thought to result in either nonsyndromic port wine stains or SWS, depending upon what stage of embryonic development is affected . Somatic mutations in GNAQ occurring at a later stage in embryogenesis may affect only precursors of vascular endothelial cells and lead to nonsyndromic port wine stains, while those occurring at an earlier stage may affect a greater variety of precursor cells and lead to SWS.
SWS is characterized by a facial capillary malformation (port wine stain) and an associated leptomeningeal capillary-venous malformation (leptomeningeal angioma) involving the brain and eye . These vascular malformations are associated with specific neurologic and ocular abnormalities.
The neurologic features of SWS may be progressive and include seizures, focal neurologic deficits, and mental retardation. Visual field defects are common when the occipital cortex is affected. These manifestations occur with variable severity. Hydrocephalus also may occur . This complication is thought to result from increased venous pressure caused by thrombosis of the deep venous channels or extensive arteriovenous anastomoses. A small proportion of patients have no neurologic abnormalities.
- Shirley MD, Tang H, Gallione CJ, et al. Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med 2013; 368:1971.
- Comi AM. Presentation, diagnosis, pathophysiology, and treatment of the neurological features of Sturge-Weber syndrome. Neurologist 2011; 17:179.
- Happle R. Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. J Am Acad Dermatol 1987; 16:899.
- Bodensteiner JB, Roach ES. Sturge-Weber syndrome: Introduction and overview. In: Sturge-Weber Syndrome, 2nd edition, Bodensteiner JB, Roach ES (Eds), Sturge-Weber Foundation, Mt. Freedom, NJ 2010.
- Fishman MA, Baram TZ. Megalencephaly due to impaired cerebral venous return in a Sturge-Weber variant syndrome. J Child Neurol 1986; 1:115.
- Maria BL, Neufeld JA, Rosainz LC, et al. Central nervous system structure and function in Sturge-Weber syndrome: evidence of neurologic and radiologic progression. J Child Neurol 1998; 13:606.
- Lee JS, Asano E, Muzik O, et al. Sturge-Weber syndrome: correlation between clinical course and FDG PET findings. Neurology 2001; 57:189.
- Sullivan TJ, Clarke MP, Morin JD. The ocular manifestations of the Sturge-Weber syndrome. J Pediatr Ophthalmol Strabismus 1992; 29:349.
- Cheng KP. Ophthalmologic manifestations of Sturge-Weber syndrome. In: Sturge-Weber Syndrome, Bodensteiner JB, Roach ES (Eds), Sturge-Weber Foundation, Mt. Freedom, NJ 1999. p.17.
- Bodensteiner JB. Sturge-Weber Syndrome. In: Vascular Birthmarks of the Head and Neck, Hochman M (Ed), Facial Plastic Surgery Clinics of North America, 2001. p.569.
- Tallman B, Tan OT, Morelli JG, et al. Location of port-wine stains and the likelihood of ophthalmic and/or central nervous system complications. Pediatrics 1991; 87:323.
- Aydin A, Cakmakçi H, Kovanlikaya A, Dirik E. Sturge-Weber syndrome without facial nevus. Pediatr Neurol 2000; 22:400.
- Comati A, Beck H, Halliday W, et al. Upregulation of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha in leptomeningeal vascular malformations of Sturge-Weber syndrome. J Neuropathol Exp Neurol 2007; 66:86.
- Sujansky E, Conradi S. Sturge-Weber syndrome: age of onset of seizures and glaucoma and the prognosis for affected children. J Child Neurol 1995; 10:49.
- Bebin EM, Gomez MR. Prognosis in Sturge-Weber disease: comparison of unihemispheric and bihemispheric involvement. J Child Neurol 1988; 3:181.
- Kaseka ML, Bitton JY, Décarie JC, Major P. Predictive Factors for Epilepsy in Pediatric Patients With Sturge-Weber Syndrome. Pediatr Neurol 2016; 64:52.
- Maton B, Krsek P, Jayakar P, et al. Medically intractable epilepsy in Sturge-Weber syndrome is associated with cortical malformation: implications for surgical therapy. Epilepsia 2010; 51:257.
- Kossoff EH, Ferenc L, Comi AM. An infantile-onset, severe, yet sporadic seizure pattern is common in Sturge-Weber syndrome. Epilepsia 2009; 50:2154.
- Bosnyák E, Behen ME, Guy WC, et al. Predictors of Cognitive Functions in Children With Sturge-Weber Syndrome: A Longitudinal Study. Pediatr Neurol 2016; 61:38.
- Pascual-Castroviejo I, Díaz-Gonzalez C, García-Melian RM, et al. Sturge-Weber syndrome: study of 40 patients. Pediatr Neurol 1993; 9:283.
- Sujansky E, Conradi S. Outcome of Sturge-Weber syndrome in 52 adults. Am J Med Genet 1995; 57:35.
- Chapieski L, Friedman A, Lachar D. Psychological functioning in children and adolescents with Sturge-Weber syndrome. J Child Neurol 2000; 15:660.
- Raches D, Hiscock M, Chapieski L. Behavioral and academic problems in children with Sturge-Weber syndrome: differences between children with and without seizures. Epilepsy Behav 2012; 25:457.
- Baselga E. Sturge-Weber syndrome. Semin Cutan Med Surg 2004; 23:87.
- Singh AD, Kaiser PK, Sears JE. Choroidal hemangioma. Ophthalmol Clin North Am 2005; 18:151.
- Phelps CD. The pathogenesis of glaucoma in Sturge-Weber syndrome. Ophthalmology 1978; 85:276.
- Miller RS, Ball KL, Comi AM, Germain-Lee EL. Growth hormone deficiency in Sturge-Weber syndrome. Arch Dis Child 2006; 91:340.
- Comi AM, Bellamkonda S, Ferenc LM, et al. Central hypothyroidism and Sturge-Weber syndrome. Pediatr Neurol 2008; 39:58.
- Truhan AP, Filipek PA. Magnetic resonance imaging. Its role in the neuroradiologic evaluation of neurofibromatosis, tuberous sclerosis, and Sturge-Weber syndrome. Arch Dermatol 1993; 129:219.
- Comi AM. Update on Sturge-Weber syndrome: diagnosis, treatment, quantitative measures, and controversies. Lymphat Res Biol 2007; 5:257.
- Puttgen KB, Lin DD. Neurocutaneous vascular syndromes. Childs Nerv Syst 2010; 26:1407.
- Bay MJ, Kossoff EH, Lehmann CU, et al. Survey of aspirin use in Sturge-Weber syndrome. J Child Neurol 2011; 26:692.
- Lance EI, Sreenivasan AK, Zabel TA, et al. Aspirin use in Sturge-Weber syndrome: side effects and clinical outcomes. J Child Neurol 2013; 28:213.
- van Emelen C, Goethals M, Dralands L, Casteels I. Treatment of glaucoma in children with Sturge-Weber syndrome. J Pediatr Ophthalmol Strabismus 2000; 37:29.
- Arzimanoglou A, Aicardi J. The epilepsy of Sturge-Weber syndrome: clinical features and treatment in 23 patients. Acta Neurol Scand Suppl 1992; 140:18.
- Comi A. Current Therapeutic Options in Sturge-Weber Syndrome. Semin Pediatr Neurol 2015; 22:295.
- Kaplan EH, Kossoff EH, Bachur CD, et al. Anticonvulsant Efficacy in Sturge-Weber Syndrome. Pediatr Neurol 2016; 58:31.
- Arzimanoglou AA, Andermann F, Aicardi J, et al. Sturge-Weber syndrome: indications and results of surgery in 20 patients. Neurology 2000; 55:1472.
- Vining EP, Freeman JM, Pillas DJ, et al. Why would you remove half a brain? The outcome of 58 children after hemispherectomy-the Johns Hopkins experience: 1968 to 1996. Pediatrics 1997; 100:163.
- Kossoff EH, Buck C, Freeman JM. Outcomes of 32 hemispherectomies for Sturge-Weber syndrome worldwide. Neurology 2002; 59:1735.
- Bourgeois M, Crimmins DW, de Oliveira RS, et al. Surgical treatment of epilepsy in Sturge-Weber syndrome in children. J Neurosurg 2007; 106:20.
- Comi AM. Sturge-Weber syndrome and epilepsy: an argument for aggressive seizure management in these patients. Expert Rev Neurother 2007; 7:951.
- GENETICS AND PATHOGENESIS
- CLINICAL FEATURES
- Port wine stain
- Leptomeningeal vascular malformation
- Intellectual disability (mental retardation)
- Behavioral problems
- Visual field defects
- Other ophthalmologic findings
- Neuroendocrine aspects
- - Indications
- Cutaneous lesions
- SUMMARY AND RECOMMENDATIONS