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Handbook of Clinical Neurology 2015Sturge-Weber syndrome is the third most common neurocutaneous disorder, after neurofibromatosis and tuberous sclerosis, and impacts approximately 1 in 20000 live births.... (Review)
Review
Sturge-Weber syndrome is the third most common neurocutaneous disorder, after neurofibromatosis and tuberous sclerosis, and impacts approximately 1 in 20000 live births. Sturge-Weber syndrome is not inherited, but rather occurs exclusively sporadically, in both males and females and in all races and ethnic backgrounds. Sturge-Weber syndrome presents at birth with a capillary malformation on the face (port-wine birthmark) with later diagnosis of abnormal vasculature in the eye and the brain which result in a range of complications. The underlying somatic mosaic mutation causing both Sturge-Weber syndrome and isolated port-wine birthmarks was recently discovered and is an activating mutation in GNAQ. When a newborn presents with a facial port-wine birthmark on the upper face, that child has a 15-50% risk of developing Sturge-Weber syndrome brain and/or eye involvement, depending on the extent of the birthmark, and close monitoring and appropriate screening is essential for early diagnosis and optimal treatment. Treatment options include laser therapy for lightening of the birthmark, eye drops and surgery for glaucoma management, and aggressive anticonvulsant treatment, low dose aspirin, and neurosurgery where necessary. Future possible treatments based upon new knowledge of the somatic mutation and downstream pathways are currently being considered and studied.
Topics: Female; GTP-Binding Protein alpha Subunits, Gq-G11; Humans; Male; Mutation; Sturge-Weber Syndrome
PubMed: 26564078
DOI: 10.1016/B978-0-444-62702-5.00011-1 -
QJM : Monthly Journal of the... Apr 2019
Topics: Calcinosis; Cerebrum; GTP-Binding Protein alpha Subunits, Gq-G11; Humans; Male; Middle Aged; Mutation; Seizures; Sturge-Weber Syndrome
PubMed: 30357409
DOI: 10.1093/qjmed/hcy246 -
The New England Journal of Medicine Aug 2017
Topics: Brain; Child; Female; Humans; Magnetic Resonance Imaging; Meninges; Sturge-Weber Syndrome
PubMed: 28854093
DOI: 10.1056/NEJMicm1700538 -
Handbook of Clinical Neurology 2016Neurocutaneous syndromes (or phakomatoses) are a diverse group of congenital disorders that encompass abnormalities of neuroectodermal and, sometimes, mesodermal... (Review)
Review
Neurocutaneous syndromes (or phakomatoses) are a diverse group of congenital disorders that encompass abnormalities of neuroectodermal and, sometimes, mesodermal development, hence commonly involving the skin, eye, and central nervous system. These are often inherited conditions and typically present in early childhood or adolescence. Some of the abnormalities and clinical symptoms may, however, be progressive, and there is an increased risk of neoplastic formation in many of the syndromes. As a group, neurocutaneous syndromes are characterized by distinctive cutaneous stigmata and neurologic symptomology, the latter often representing the most devastating and debilitating features of these diseases. Many of these syndromes are markedly heterogeneous in nature as they affect many organ systems. Given the incurable nature of these conditions and the broad spectrum of pathologies they comprise, treatments vary on a case-by-case basis and tend to be palliative rather than curative. With the advances in molecular genetics, however, greater understanding of biologic functions of the gene products and the correlative phenotypic expression is being attained, and this knowledge may guide future therapeutic developments. This chapter focuses on the cutaneous and neurologic pathology with emphasis on neuroimaging of selective neurocutaneous syndromes, including tuberous sclerosis, Sturge-Weber syndrome, Klippel-Trenaunay syndrome, ataxia-telangiectasia, and incontinentia pigmenti.
Topics: Brain; Humans; Magnetic Resonance Imaging; Neurocutaneous Syndromes
PubMed: 27432683
DOI: 10.1016/B978-0-444-53485-9.00027-1 -
Handbook of Clinical Neurology 2015PHACE(S) syndrome is a neurocutaneous disorder of unknown etiology. The acronym refers to the commonest features of PHACE: posterior fossa malformations, large facial... (Review)
Review
PHACE(S) syndrome is a neurocutaneous disorder of unknown etiology. The acronym refers to the commonest features of PHACE: posterior fossa malformations, large facial hemangiomas, cerebral arterial anomalies, cardiovascular anomalies, and eye anomalies. When ventral developmental defects such as sternal clefting or supraumbilical raphe occur, the PHACES acronym may be used. The hallmark feature of PHACE is the presence of one or more large facial infantile hemangiomas that occupy at least one facial segment. Infantile hemangiomas differ from the capillary malformation (port wine stain) of Sturge-Weber syndrome, and the arteriovenous malformation of Wyburn-Mason syndrome, distinguishing PHACE syndrome from other neurocutaneous disorders with red birthmarks. The true incidence of PHACE has not yet been established. Girls are more commonly affected than boys. Cerebral vascular anomalies are probably the most common extracutaneous feature. Given that several organ systems are involved, a multidisciplinary approach to disease surveillance and treatment is advised.
Topics: Abnormalities, Multiple; Aortic Coarctation; Eye Abnormalities; Female; Hemangioma; Humans; Male; Neurocutaneous Syndromes
PubMed: 26564079
DOI: 10.1016/B978-0-444-62702-5.00012-3 -
Brain and Nerve = Shinkei Kenkyu No... Apr 2019The cutaneous findings associated with Sturge-Weber syndrome (SWS) are characterized by a port-wine stain at the site of the first branching of the trigeminal nerve....
The cutaneous findings associated with Sturge-Weber syndrome (SWS) are characterized by a port-wine stain at the site of the first branching of the trigeminal nerve. Recently, a new vascular classification for the port-wine stain is proposed in association with SWS. There is no consensus regarding the screening of SWS, but suspected cases of SWS are recommended for early referral to ophthalmologists. Magnetic resonance imaging (MRI) of the brain in infants, when they are younger than 6 months, leaves the possibility of false-negatives of SWS.
Topics: Brain; Humans; Infant; Magnetic Resonance Imaging; Port-Wine Stain; Skin; Sturge-Weber Syndrome; Trigeminal Nerve
PubMed: 30988226
DOI: 10.11477/mf.1416201281 -
Continuum (Minneapolis, Minn.) Feb 2018This article presents an up-to-date summary of the genetic etiology, diagnostic criteria, clinical features, and current management recommendations for the most common... (Review)
Review
PURPOSE OF REVIEW
This article presents an up-to-date summary of the genetic etiology, diagnostic criteria, clinical features, and current management recommendations for the most common neurocutaneous disorders encountered in clinical adult and pediatric neurology practices.
RECENT FINDINGS
The phakomatoses are a phenotypically and genetically diverse group of multisystem disorders that primarily affect the skin and central nervous system. A greater understanding of the genetic and biological underpinnings of numerous neurocutaneous disorders has led to better clinical characterization, more refined diagnostic criteria, and improved treatments in neurofibromatosis type 1, Legius syndrome, neurofibromatosis type 2, Noonan syndrome with multiple lentigines, tuberous sclerosis complex, Sturge-Weber syndrome, and incontinentia pigmenti.
SUMMARY
Neurologists require a basic knowledge of and familiarity with a wide variety of neurocutaneous disorders because of the frequent involvement of the central and peripheral nervous systems. A simple routine skin examination can often open a broad differential diagnosis and lead to improved patient care.
Topics: Adult; Child; Female; Humans; Male; Neurocutaneous Syndromes
PubMed: 29432239
DOI: 10.1212/CON.0000000000000562 -
The Journal of Clinical Investigation Apr 2024Capillary malformation (CM), or port wine birthmark, is a cutaneous congenital vascular anomaly that occurs in 0.1%-2% of newborns. Patients with a CM localized on the... (Review)
Review
Capillary malformation (CM), or port wine birthmark, is a cutaneous congenital vascular anomaly that occurs in 0.1%-2% of newborns. Patients with a CM localized on the forehead have an increased risk of developing a neurocutaneous disorder called encephalotrigeminal angiomatosis or Sturge-Weber syndrome (SWS), with complications including seizure, developmental delay, glaucoma, and vision loss. In 2013, a groundbreaking study revealed causative activating somatic mutations in the gene (GNAQ) encoding guanine nucleotide-binding protein Q subunit α (Gαq) in CM and SWS patient tissues. In this Review, we discuss the disease phenotype, the causative GNAQ mutations, and their cellular origin. We also present the endothelial Gαq-related signaling pathways, the current animal models to study CM and its complications, and future options for therapeutic treatment. Further work remains to fully elucidate the cellular and molecular mechanisms underlying the formation and maintenance of the abnormal vessels.
Topics: Infant, Newborn; Animals; Humans; Glaucoma; Models, Animal; Mutation; Capillaries; Vascular Malformations
PubMed: 38618955
DOI: 10.1172/JCI172842 -
Handbook of Clinical Neurology 2018The primary neurologic involvement in both von Hippel-Lindau (VHL) disease and Sturge-Weber syndrome (SWS) is vascular tumor/vascular malformation, but molecular... (Review)
Review
The primary neurologic involvement in both von Hippel-Lindau (VHL) disease and Sturge-Weber syndrome (SWS) is vascular tumor/vascular malformation, but molecular pathogenesis, long-term symptom evolution, and treatment are quite different. VHL is caused by dominant inherited or de novo germline mutations, while SWS is caused by somatic mosaicism. A diagnosis of VHL carries substantial cancer risk, while the clinical issues in SWS are primarily related to the consequences of the intracranial vascular abnormalities.
Topics: Germ-Line Mutation; Humans; Sturge-Weber Syndrome; von Hippel-Lindau Disease
PubMed: 29478617
DOI: 10.1016/B978-0-444-64076-5.00053-3 -
Pediatric Neurology Feb 2021Sturge-Weber syndrome is a rare neurovascular disorder associated with capillary malformation, seizures, cognitive impairments, and stroke-like episodes (SLEs), arising...
BACKGROUND
Sturge-Weber syndrome is a rare neurovascular disorder associated with capillary malformation, seizures, cognitive impairments, and stroke-like episodes (SLEs), arising from a somatic activating mutation in GNAQ. Studies suggest this mutation may cause hyperactivation of the mammalian target of rapamycin pathway. Sirolimus is an mammalian target of rapamycin inhibitor studied in other vascular anomalies and a potentially promising therapy in Sturge-Weber syndrome.
METHODS
Ten patients with Sturge-Weber syndrome brain involvement and cognitive impairments were enrolled. Oral sirolimus was taken for six months (maximum dose: 2 mg/day, target trough level: 4-6 ng/mL). Neuropsychological testing, electroencephalography, and port-wine score were performed at baseline and after six months on sirolimus. Neuroquality of life, adverse events, and Sturge-Weber Syndrome Neurological Score (neuroscore) were recorded at each visit.
RESULTS
Sirolimus was generally well tolerated; one subject withdrew early. Adverse events considered related to sirolimus were mostly (15/16) grade 1. A significant increase in processing speed was seen in the overall group (P = 0.031); five of nine patients with available data demonstrated statistically rare improvement in processing speed. Improvements were seen in the neuroquality of life subscales measuring anger (P = 0.011), cognitive function (P = 0.015), and depression (P = 0.046). Three subjects experiencing SLEs before and during the study reported shortened recovery times while on sirolimus.
CONCLUSIONS
Sirolimus was well tolerated in individuals with Sturge-Weber syndrome and may be beneficial for cognitive impairments, especially in patients with impaired processing speed or a history of SLE. A future, randomized, placebo-controlled trial of sirolimus in patients with Sturge-Weber syndrome is needed to further understand these potentially beneficial effects.
Topics: Adolescent; Adult; Child; Child, Preschool; Cognitive Dysfunction; Electroencephalography; Female; Humans; Male; Protein Kinase Inhibitors; Sirolimus; Sturge-Weber Syndrome; Young Adult
PubMed: 33316689
DOI: 10.1016/j.pediatrneurol.2020.10.013