Sturge-Weber syndrome

Summary

Sturge-Weber syndrome (MONDO:0008501) is a disease caused by GNAQ (GenCC Strong), with 1 cohort gene and 16 clinical trials. Top therapeutic interventions include timolol, sirolimus, and cannabidiol.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Causal gene: GNAQ (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 4
• Phenotypes (HPO): 51
• Clinical trials: 16

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	3.5	Europe	Validated
Point prevalence	1-9 / 100 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

51 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000996	Facial capillary hemangioma	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0005306	Capillary hemangioma	Very frequent (80-99%)
HP:0000486	Strabismus	Frequent (30-79%)
HP:0000501	Glaucoma	Frequent (30-79%)
HP:0000648	Optic atrophy	Frequent (30-79%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0000750	Delayed speech and language development	Frequent (30-79%)
HP:0001123	Visual field defect	Frequent (30-79%)
HP:0001249	Intellectual disability	Frequent (30-79%)
HP:0001297	Stroke	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0002315	Headache	Frequent (30-79%)
HP:0007018	Attention deficit hyperactivity disorder	Frequent (30-79%)
HP:0012019	Lens luxation	Frequent (30-79%)
HP:0012222	Arachnoid hemangiomatosis	Frequent (30-79%)
HP:0012469	Infantile spasms	Frequent (30-79%)
HP:0012758	Neurodevelopmental delay	Frequent (30-79%)
HP:0100659	Abnormality of the cerebral vasculature	Frequent (30-79%)
HP:0100774	Hyperostosis	Occasional (5-29%)
HP:0200026	Ocular pain	Occasional (5-29%)
HP:0000212	Gingival overgrowth	Occasional (5-29%)
HP:0000238	Hydrocephalus	Occasional (5-29%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0000364	Hearing abnormality	Occasional (5-29%)
HP:0000504	Abnormality of vision	Occasional (5-29%)
HP:0000524	Conjunctival telangiectasia	Occasional (5-29%)
HP:0000541	Retinal detachment	Occasional (5-29%)
HP:0000557	Buphthalmos	Occasional (5-29%)
HP:0000572	Visual loss	Occasional (5-29%)
HP:0000610	Abnormal choroid morphology	Occasional (5-29%)
HP:0000612	Iris coloboma	Occasional (5-29%)
HP:0000618	Blindness	Occasional (5-29%)
HP:0000689	Dental malocclusion	Occasional (5-29%)
HP:0000729	Autistic behavior	Occasional (5-29%)
HP:0001100	Heterochromia iridis	Occasional (5-29%)
HP:0001131	Corneal dystrophy	Occasional (5-29%)
HP:0002015	Dysphagia	Occasional (5-29%)
HP:0002120	Cerebral cortical atrophy	Occasional (5-29%)
HP:0002204	Pulmonary embolism	Occasional (5-29%)
HP:0002308	Chiari malformation	Occasional (5-29%)
HP:0002360	Sleep abnormality	Occasional (5-29%)
HP:0002514	Cerebral calcification	Occasional (5-29%)
HP:0004936	Venous thrombosis	Occasional (5-29%)
HP:0007872	Choroidal hemangioma	Occasional (5-29%)
HP:0008046	Abnormal retinal vascular morphology	Occasional (5-29%)
HP:0009926	Epiphora	Occasional (5-29%)
HP:0011787	Central hypothyroidism	Occasional (5-29%)
HP:0012377	Hemianopia	Occasional (5-29%)
HP:0034323	Reduced circulating growth hormone concentration	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Sturge-Weber syndrome
Mondo ID	MONDO:0008501
MeSH	D013341
OMIM	185300
Orphanet	3205
DOID	DOID:0111563
ICD-11	1173035836
NCIT	C3391
SNOMED CT	19886006
UMLS	C0038505
MedGen	21361
GARD	0007706
MedDRA	10042265, 10057653
NORD	1741
Is cancer (heuristic)	no

Also known as: encephalofacial angiomatosis · encephalotrigeminal angiomatosis · encephalotrigeminal syndrome · fourth phacomatosis · leptomeningeal angiomatosis · meningeal capillary angiomatosis · Sturge Weber Syndrome · Sturge Weber syndrome · Sturge-Weber disease · Sturge-Weber syndrome · Sturge-Weber syndrome, somatic, mosaic · Sturge-Weber-Dimitri syndrome · Sturge-Weber-Krabbe angiomatosis · Sturge-Weber-Krabbe syndrome · SWS · SWS type I - Facial and leptomeningeal angiomas · SWS type II - Facial angioma alone, no CNS involvement · SWS type III - isolated leptomeningeal angiomas

Data availability: 4 ClinVar variants · 3 GenCC gene-disease records · 6 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › Sturge-Weber syndrome

Related subtypes (119): ptosis, eye accommodation disease, corneal disorder, asthenopia, lens disorder, keratomalacia, scleral disorder, ocular siderosis, coloboma, luxation of globe, mucopolysaccharidosis type 1, lacrimal apparatus disorder, Foster-Kennedy syndrome, anterior dislocation of lens, uveal disorder, eyelid disorder, ocular hypotension, scotoma, exophthalmos, ophthalmia nodosa, eye degenerative disorder, refractive error, glaucoma, retinal disorder, eye allergy, ocular vascular disorder, optic neuritis, conjunctival disorder, ocular hypertension, Tietz syndrome, Alagille syndrome, glaucoma-sleep apnea syndrome, Marshall syndrome, microcornea-glaucoma-absent frontal sinuses syndrome, nail-patella syndrome, oculodentodigital dysplasia, piebaldism, cerebrotendinous xanthomatosis, ocular cystinosis, alpha-mannosidosis, megalocornea-intellectual disability syndrome, mucolipidosis type IV, mucopolysaccharidosis type 6, Netherton syndrome, galactosialidosis, Niemann-Pick disease type A, ocular motor apraxia, Cogan type, Peters plus syndrome, isolated Pierre-Robin syndrome, ectodermal dysplasia-blindness syndrome, Sandhoff disease, SHORT syndrome, Sjogren-Larsson syndrome, Smith-Lemli-Opitz syndrome, Tay-Sachs disease, tyrosinemia type II, Ito hypomelanosis, X-linked cone dysfunction syndrome with myopia, red color blindness, oculocerebrorenal syndrome, Lowry-MacLean syndrome, pigment dispersion syndrome, hereditary hyperferritinemia with congenital cataracts, dyssegmental dysplasia-glaucoma syndrome, mevalonic aciduria, familial cavitary optic disk anomaly, blindness - scoliosis - arachnodactyly syndrome, fatty acyl-CoA reductase 1 deficiency, microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome, neurotrophic keratopathy, Cogan syndrome, atopic keratoconjunctivitis, rhizomelic chondrodysplasia punctata, Ehlers-Danlos syndrome, kyphoscoliotic type 1, IRVAN syndrome, Rothmund-Thomson syndrome type 2, microcornea-corectopia-macular hypoplasia syndrome, isolated anophthalmia-microphthalmia syndrome, Spasmus nutans, toxic maculopathy due to antimalarial drugs, syndromic recessive X-linked ichthyosis, acute zonal occult outer retinopathy, acute annular outer retinopathy, phakomatosis pigmentovascularis, lamellar ichthyosis, idiopathic linear interstitial keratitis, chondroectodermal dysplasia with night blindness, galactosemia, GM1 gangliosidosis, Gaucher disease, visual snow syndrome, extensive peripapillary myelinated nerve fibers, IgG4-related ophthalmic disorder, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, vernal keratoconjunctivitis, Gardner syndrome, anterior segment dysgenesis, isolated ankyloblepharon filiforme adnatum, hereditary optic neuropathy, essential strabismus, Axenfeld anomaly, eye neoplasm, isolated blepharochalasis, punctate inner choroidopathy, eye infectious disorder, vitreous body disorder, 9q33.3q34.11 microdeletion syndrome, autoimmune/inflammatory optic neuropathy, LTBP2-related ocular dysgenesis, ocular growth disorder, ocular dysgenesis caused by defects in PAX6 regulation, choroidal neovascularization, anterior segment developmental abnormality with extraocular manifestations, congenital optic disk excavation, neuroocular syndrome, isolated angioid streaks, multiple evanescent white dot syndrome, stellate multiform amelanotic choroidopathy, macular telangiectasia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

4 retrieved; paginated sample, class counts are floors:

2 pathogenic/likely pathogenic, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1691370	NM_002072.5(GNAQ):c.143G>T (p.Gly48Val)	GNAQ	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
375955	NM_002072.5(GNAQ):c.626A>T (p.Gln209Leu)	GNAQ	Pathogenic	criteria provided, single submitter
375956	NM_002072.5(GNAQ):c.626A>G (p.Gln209Arg)	GNAQ	Pathogenic	criteria provided, single submitter
50853	NM_002072.5(GNAQ):c.548G>A (p.Arg183Gln)	GNAQ	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GNAQ	Strong	Autosomal dominant	Sturge-Weber syndrome	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GNAQ	Orphanet:3205	Sturge-Weber syndrome
GNAQ	Orphanet:39044	Uveal melanoma
GNAQ	Orphanet:624	Familial multiple nevi flammei
GNAQ	Orphanet:675359	Anastomosing haemangioma
GNAQ	Orphanet:79483	Phakomatosis cesioflammea

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GNAQ	HGNC:4390	ENSG00000156052	P50148	Guanine nucleotide-binding protein G(q) subunit alpha	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GNAQ	Guanine nucleotide-binding protein G(q) subunit alpha	Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GNAQ	Other/Unknown	no		Gprotein_alpha_Q, Gprotein_alpha_su, GproteinA_insert

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
CA1 field of hippocampus	1
dorsal motor nucleus of vagus nerve	1
postcentral gyrus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GNAQ	302	ubiquitous	marker	CA1 field of hippocampus, dorsal motor nucleus of vagus nerve, postcentral gyrus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GNAQ	3,480

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNAQ	P50148	37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion	1	1427.5×	0.004	GNAQ
Acetylcholine regulates insulin secretion	1	1142.0×	0.004	GNAQ
G-protein activation	1	475.8×	0.004	GNAQ
Thromboxane signalling through TP receptor	1	475.8×	0.004	GNAQ
ADP signalling through P2Y purinoceptor 1	1	456.8×	0.004	GNAQ
Thrombin signalling through proteinase activated receptors (PARs)	1	356.9×	0.004	GNAQ
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	1	356.9×	0.004	GNAQ
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	1	300.5×	0.005	GNAQ
PLC beta mediated events	1	265.6×	0.005	GNAQ
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	160.8×	0.007	GNAQ
G alpha (q) signalling events	1	57.4×	0.017	GNAQ

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
phospholipase C-activating G protein-coupled glutamate receptor signaling pathway	1	4213.0×	0.002	GNAQ
phospholipase C-activating serotonin receptor signaling pathway	1	2808.7×	0.002	GNAQ
entrainment of circadian clock	1	2808.7×	0.002	GNAQ
regulation of platelet activation	1	2808.7×	0.002	GNAQ
sensory perception of itch	1	1872.4×	0.002	GNAQ
response to prostaglandin E	1	1404.3×	0.002	GNAQ
phototransduction, visible light	1	1296.3×	0.002	GNAQ
G protein-coupled acetylcholine receptor signaling pathway	1	1053.2×	0.002	GNAQ
glutamate receptor signaling pathway	1	936.2×	0.002	GNAQ
cellular response to acidic pH	1	732.7×	0.002	GNAQ
mast cell degranulation	1	624.1×	0.003	GNAQ
regulation of canonical Wnt signaling pathway	1	543.6×	0.003	GNAQ
hormone-mediated signaling pathway	1	401.2×	0.003	GNAQ
blood coagulation	1	173.7×	0.007	GNAQ
neuropeptide signaling pathway	1	172.0×	0.007	GNAQ
phospholipase C-activating G protein-coupled receptor signaling pathway	1	131.7×	0.009	GNAQ
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	113.1×	0.009	GNAQ
protein stabilization	1	66.9×	0.015	GNAQ

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Cannabidiol, Everolimus, Sirolimus.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GNAQ	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GNAQ	27	Binding:27

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GNAQ

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GNAQ	27	—

Clinical trials & evidence

Clinical trials

Clinical trials: 16.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6
PHASE2	5
PHASE1	2
PHASE4	1
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04999618	PHASE4	COMPLETED	A New Approach in Laser Surgery Using the Regenerative Solution in Children Diagnosed With Vascular Pathology
NCT03047980	PHASE2/PHASE3	COMPLETED	Trial of Sirolimus for Cognitive Impairment in Sturge-Weber Syndrome
NCT01997255	PHASE2	WITHDRAWN	Adjunctive Everolimus (RAD 001) Therapy for Epilepsy in Children With Sturge-Weber Syndrome (SWS)
NCT02080624	PHASE2	COMPLETED	Efficacy and Safety Study of Topical Rapamycin Associated With Pulsed Dye Laser in Patients With Sturge-Weber Syndrome
NCT02332655	PHASE1/PHASE2	COMPLETED	Cannabidiol Expanded Access Study in Medically Refractory Sturge-Weber Syndrome
NCT04447846	PHASE2	COMPLETED	Novel Cognitive Treatment Targets for Epidiolex in Sturge- Weber Syndrome
NCT04947124	PHASE2	COMPLETED	A Study to Determine the Safety and Tolerability of 2 Concentrations of QLS-101
NCT05495269	PHASE2	COMPLETED	Safety and Tolerability Study of QLS-101 in Adolescents With Sturge-Weber Syndrome (SWS)-Related Glaucoma Due to Elevated Episcleral Venous Pressure (EVP)
NCT00639730	PHASE1	COMPLETED	Use of the Atkins Diet for Children With Sturge Weber Syndrome
NCT01533376	PHASE1	TERMINATED	Treatment of Port-wine Mark in Sturge-Weber Syndrome Using Topical Timolol
NCT01425944	Not specified	ACTIVE_NOT_RECRUITING	Innovative Approaches to Gauge Progression of Sturge-Weber Syndrome
NCT04517565	Not specified	ACTIVE_NOT_RECRUITING	Longitudinal Neuroimaging in Sturge-Weber Syndrome
NCT04717427	Not specified	RECRUITING	Longitudinal Studies to Identify Biomarkers for Sturge-Weber Syndrome
NCT01345305	Not specified	COMPLETED	Biomarker Development in Sturge-Weber Syndrome
NCT04344626	Not specified	WITHDRAWN	Use of a Tonometer to Identify Epileptogenic Lesions During Pediatric Epilepsy Surgery
NCT07327164	Not specified	COMPLETED	Precision Medicine for Neurocutaneous Syndromes in Western China

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TIMOLOL	4	3
SIROLIMUS	4	2
CANNABIDIOL	4	1
CHEMBL1744069	0	1