{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T17:14:22Z","timestamp":1783617262618,"version":"3.55.0"},"reference-count":92,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Oradea"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Neurocutaneous syndromes (NCS), including neurofibromatosis type 1 (NF1), tuberous sclerosis complex (TSC), and Sturge\u2013Weber syndrome (SWS), are rare neurodevelopmental disorders frequently associated with epilepsy, cognitive impairment, and behavioural difficulties. Although caused by different genetic alterations, these disorders share biological mechanisms that influence brain development, neuronal connectivity, and network excitability. Beyond being a common neurological manifestation, epilepsy is increasingly recognized as an important factor influencing cognitive and behavioural outcomes in neurocutaneous syndromes. Methods: This narrative review summarizes current evidence on the relationship between epilepsy, cognitive dysfunction, and behavioural manifestations in major neurocutaneous syndromes. Attention is given to epileptogenic mechanisms, shared molecular pathways, and factors influencing long-term neurodevelopmental outcomes. Results: Epilepsy is consistently associated with cognitive and behavioural outcomes in neurocutaneous syndromes, particularly in disorders characterized by early-onset and treatment-resistant seizures. Early seizure onset, poor seizure control, and persistent network dysfunction have been associated with intellectual disability, executive dysfunction, attention deficits, autism spectrum features, and impaired adaptive functioning. In TSC and SWS, epilepsy burden is strongly associated with cognitive outcome, particularly in interaction with underlying structural, vascular, and molecular abnormalities. In neurofibromatosis type 1, cognitive and behavioural difficulties are more often related to altered neuronal connectivity and dysregulated signalling pathways, although epilepsy may further contribute to neurodevelopmental impairment in a subset of patients. Despite their distinct genetic origins, these disorders converge on dysregulated RAS\/MAPK, PI3K\/AKT\/mTOR, and G\u03b1q-mediated signalling pathways that influence both epileptogenesis and brain development. Conclusions: Despite their distinct genetic origins, major neurocutaneous syndromes converge on common pathways linking epilepsy, network dysfunction, and neurodevelopmental impairment. Understanding how these processes interact may facilitate earlier intervention and more accurate prognostic assessment, ultimately improving long-term outcomes for affected children.<\/jats:p>","DOI":"10.3390\/children13070912","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T16:16:44Z","timestamp":1783613804000},"page":"912","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epilepsy, Cognitive, and Behavioral Outcomes in Neurocutaneous Syndromes: A Comparative Review of NF1, TSC, and Sturge\u2013Weber Syndrome"],"prefix":"10.3390","volume":"13","author":[{"given":"Aurora Alexandra","family":"Jurca","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Pharmacy, University of Oradea, Universitatii Street 1, 410081 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2476-9706","authenticated-orcid":false,"given":"Romana","family":"Vulturar","sequence":"additional","affiliation":[{"name":"Discipline of Cell and Molecular Biology, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 6, Pasteur St., 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adina","family":"Chis","sequence":"additional","affiliation":[{"name":"Discipline of Cell and Molecular Biology, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 6, Pasteur St., 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Lucretia","family":"Trandafir","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, University of Oradea, Universitatii Street 1, 410081 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8442-6791","authenticated-orcid":false,"given":"Codru\u021ba Diana","family":"Petchesi","sequence":"additional","affiliation":[{"name":"Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, Universitatii Street 1, 410081 Oradea, Romania"},{"name":"Regional Center of Medical Genetics Bihor (Part of ERN-ITHACA), County Emergency Clinical Hospital Oradea, 410469 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6276-0094","authenticated-orcid":false,"given":"Kinga","family":"Kozma","sequence":"additional","affiliation":[{"name":"Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, Universitatii Street 1, 410081 Oradea, Romania"},{"name":"Regional Center of Medical Genetics Bihor (Part of ERN-ITHACA), County Emergency Clinical Hospital Oradea, 410469 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3901-615X","authenticated-orcid":false,"given":"Emilia","family":"Severin","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Medicine and Pharmacy \u201cCarol Davila\u201d Bucharest, Dionisie Lupu Street, Number 37, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7507-5072","authenticated-orcid":false,"given":"Ramona","family":"Hodisan","sequence":"additional","affiliation":[{"name":"Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, Universitatii Street 1, 410081 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Maria","family":"Jurca","sequence":"additional","affiliation":[{"name":"Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, Universitatii Street 1, 410081 Oradea, Romania"},{"name":"Regional Center of Medical Genetics Bihor (Part of ERN-ITHACA), County Emergency Clinical Hospital Oradea, 410469 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona Ioana","family":"Vicas","sequence":"additional","affiliation":[{"name":"Department of Food Engineering, University of Oradea, 26 Gen. Magheru St., 410048 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanziana Iulia","family":"Jurca","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, University of Oradea, Universitatii Street 1, 410081 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru Daniel","family":"Jurca","sequence":"additional","affiliation":[{"name":"Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, Universitatii Street 1, 410081 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1007\/s00381-020-04758-5","article-title":"Introduction to Phacomatoses (Neurocutaneous Disorders) in Childhood","volume":"36","author":"Ruggieri","year":"2020","journal-title":"Childs Nerv. Syst."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101150","DOI":"10.1016\/j.spen.2024.101150","article-title":"Genetic Principles Related to Neurocutaneous Disorders","volume":"51","author":"Ferrante","year":"2024","journal-title":"Semin. Pediatr. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1528-1167.2005.00353.x","article-title":"Neurocutaneous syndromes and epilepsy-issues in diagnosis and management","volume":"46","author":"Cross","year":"2005","journal-title":"Epilepsia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"351","DOI":"10.5414\/CN111425","article-title":"Renal Involvement in Genetic Neurocutaneous Syndromes","volume":"102","author":"Izzedine","year":"2024","journal-title":"Clin. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1038\/nn.3546","article-title":"mTOR complexes in neurodevelopmental and neuropsychiatric disorders","volume":"16","author":"Monteggia","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kioutchoukova, N., Lee, A., Chen, T., Gomez, C., Patel, R., Hossain, S., Stein, J., Koo, B., and Sun, Y. (2024). Neurocutaneous Diseases: Diagnosis, Management, and Treatment. J. Clin. Med., 13.","DOI":"10.20944\/preprints202401.1301.v1"},{"key":"ref_7","first-page":"563","article-title":"Cardiofaciocutaneous Syndrome\u2014A Longitudinal Study of a Case over 33 Years: Case Report and Review of the Literature","volume":"62","author":"Iuhas","year":"2021","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1080\/09297049.2010.542746","article-title":"Assessment of Executive Function and Attention in Children with Neurofibromatosis Type 1: Relationships Between Cognitive Measures and Real-World Behavior","volume":"17","author":"Payne","year":"2011","journal-title":"Child Neuropsychol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1017\/S1355617718000383","article-title":"Systematic Review and Meta-Analysis of Executive Functions in Preschool and School-Age Children with Neurofibromatosis Type 1","volume":"24","author":"Beaussart","year":"2018","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"ref_10","first-page":"973","article-title":"Learning disabilities in children with neurofibromatosis type 1: Subtypes, cognitive profile, and attention-deficit-hyperactivity disorder","volume":"48","author":"Hyman","year":"2006","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1186\/s13023-024-03454-w","article-title":"Neurocognitive functioning in adults with neurofibromatosis type 1- a nationwide population-based study","volume":"19","author":"Doser","year":"2024","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.pediatrneurol.2018.12.002","article-title":"Physical and Family History Variables Associated with Neurological and Cognitive Development in Sturge-Weber Syndrome","volume":"96","author":"Day","year":"2019","journal-title":"Pediatr. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.pediatrneurol.2013.08.001","article-title":"Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference","volume":"49","author":"Northrup","year":"2013","journal-title":"Pediatr. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1212\/01.wnl.0000280579.04974.c0","article-title":"Cognitive impairment in tuberous sclerosis complex is a multifactorial condition","volume":"70","author":"Jansen","year":"2008","journal-title":"Neurology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ejpn.2021.07.005","article-title":"Neurological presentations and cognitive outcome in Sturge-Weber syndrome","volume":"34","author":"Powell","year":"2021","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.pediatrneurol.2020.12.012","article-title":"Extent of Leptomeningeal Capillary Malformation is Associated With Severity of Epilepsy in Sturge-Weber Syndrome","volume":"117","author":"Sugano","year":"2021","journal-title":"Pediatr. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1111\/j.1469-8749.2012.04357.x","article-title":"Does Attention-Deficit\/Hyperactivity Disorder Exacerbate Executive Dysfunction in Children with Neurofibromatosis Type 1?","volume":"54","author":"Payne","year":"2012","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"147","DOI":"10.4103\/JME.JME_80_20","article-title":"Neurocutaneous Syndromes: Imaging of Systemic Manifestations","volume":"2","author":"Varghese","year":"2021","journal-title":"J. Med. Evid."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"M\u00fcller, A.R., Luijten, M.A.J., Haverman, L., de Ranitz-Greven, W.L., Janssens, P., Rietman, A.B., Hoopen, L.W.T., de Graaff, L.C.G., de Wit, M.-C., and Jansen, A.C. (2023). Correction: Understanding the Impact of Tuberous Sclerosis Complex: Development and Validation of the TSC-PROM. BMC Med., 21.","DOI":"10.1186\/s12916-023-03092-2"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1038\/s41436-021-01170-5","article-title":"Revised Diagnostic Criteria for Neurofibromatosis Type 1 and Legius Syndrome: An International Consensus Recommendation","volume":"23","author":"Legius","year":"2021","journal-title":"Genet. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/0092-8674(90)90024-9","article-title":"The Neurofibromatosis Type 1 Gene Encodes a Protein Related to GAP","volume":"62","author":"Xu","year":"1990","journal-title":"Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1038\/s41388-021-02156-y","article-title":"Neurofibromin and suppression of tumorigenesis: Beyond the GAP","volume":"41","author":"Mo","year":"2022","journal-title":"Oncogene"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Upadhyaya, M., and Cooper, D.N. (2012). Neurofibromatosis Type 1: Molecular and Cellular Biology, Springer.","DOI":"10.1007\/978-3-642-32864-0"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Van Trigt, W.K., Kelly, K.M., and Hughes, C.C.W. (2022). GNAQ mutations drive port wine birthmark-associated Sturge-Weber syndrome: A review of pathobiology, therapies, and current models. Front. Hum. Neurosci., 16.","DOI":"10.3389\/fnhum.2022.1006027"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1128\/MMBR.00031-10","article-title":"Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases","volume":"75","author":"Cargnello","year":"2011","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.drup.2007.11.003","article-title":"Targeting the PI3K\/Akt\/mTOR pathway: Effective combinations and clinical considerations","volume":"11","author":"LoPiccolo","year":"2008","journal-title":"Drug Resist. Updates"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/exd.13212","article-title":"Neurofibromatosis Type 1 (NF1) Gene: Beyond Caf\u00e9 Au Lait Spots and Dermal Neurofibromas","volume":"26","author":"Peltonen","year":"2017","journal-title":"Exp. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1212\/01.wnl.0000179303.72345.ce","article-title":"The Nature and Frequency of Cognitive Deficits in Children with Neurofibromatosis Type 1","volume":"65","author":"Hyman","year":"2005","journal-title":"Neurology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/(SICI)1096-8628(19990326)89:1<45::AID-AJMG9>3.0.CO;2-J","article-title":"Cognitive Impairment in Neurofibromatosis Type 1","volume":"89","author":"Ozonoff","year":"1999","journal-title":"Am. J. Med. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1002\/ajmg.a.62773","article-title":"A systematic review and meta-analysis of intellectual, neuropsychological, and psychoeducational functioning in neurofibromatosis type 1","volume":"188","author":"Crow","year":"2022","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ejpn.2020.07.003","article-title":"Are Morphological and Structural MRI Characteristics Related to Specific Cognitive Impairments in Neurofibromatosis Type 1 Children?","volume":"28","author":"Baudou","year":"2020","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1080\/13803395.2021.1893277","article-title":"Executive Functions in Preschool-Aged Children with Neurofibromatosis Type 1: Value for Early Assessment","volume":"43","author":"Barbarot","year":"2021","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Karlsgodt, K.H., Rosser, T., Lutkenhoff, E.S., and Cannon, T.D. (2012). Alterations in White Matter Microstructure in Neurofibromatosis-1. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047854"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s11689-024-09565-6","article-title":"Unraveling Neuronal and Metabolic Alterations in Neurofibromatosis Type 1","volume":"16","author":"Botero","year":"2024","journal-title":"J. Neurodev. Disord."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1177\/0883073811423974","article-title":"Developmental Delays in Children with Neurofibromatosis Type 1","volume":"27","author":"Soucy","year":"2012","journal-title":"J. Child Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1001\/jamapsychiatry.2016.2600","article-title":"Disease Burden and Symptom Structure of Autism in Neurofibromatosis Type 1: A Study of the International NF1-ASD Consortium Team (INFACT)","volume":"73","author":"Morris","year":"2016","journal-title":"JAMA Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1002\/ajmg.b.32414","article-title":"Executive Functioning Deficits in Children with Neurofibromatosis Type 1: The Influence of Intellectual and Social Functioning","volume":"171B","author":"Plasschaert","year":"2016","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"70","DOI":"10.51847\/QG2iHRJqUL","article-title":"The Surprises of Molecular Testing in Neurofibromatosis Type 1: Rare Association between Two Mutational Variants","volume":"15","author":"Jurca","year":"2024","journal-title":"Pharmacophore 2"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1111\/dmcn.14144","article-title":"Adaptive functioning in children with neurofibromatosis type 1: Relationship to cognition, behavior, and magnetic resonance imaging","volume":"61","author":"Eby","year":"2019","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/j.1469-8749.2012.04399.x","article-title":"Behaviour in children with neurofibromatosis type 1: Cognition, executive function, attention, emotion, and social competence","volume":"55","author":"Lehtonen","year":"2013","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.jpeds.2008.08.045","article-title":"Health-Related Quality of Life in Children with Neurofibromatosis Type 1: Contribution of Demographic Factors, Disease-Related Factors, and Behavior","volume":"154","author":"Krab","year":"2009","journal-title":"J. Pediatr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1186\/s13023-023-02959-0","article-title":"A Single-Center Observational Study on Long-Term Neurodevelopmental Outcomes in Children with Tuberous Sclerosis Complex","volume":"18","author":"Mammadova","year":"2023","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Jurca, A., Pop, S., Vesa, C.M., Jurca, A.D., and Jurca, C.M. (2025). Tuberous Sclerosis Complex: New Insights into Pathogenesis and Therapeutic Breakthroughs. Life, 15.","DOI":"10.3390\/life15030368"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1186\/s13023-018-0901-8","article-title":"TSC-Associated Neuropsychiatric Disorders (TAND): Findings from the TOSCA Natural History Study","volume":"13","author":"Belousova","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13023-016-0553-5","article-title":"TuberOus SClerosis Registry to Increase Disease Awareness (TOSCA)\u2014Baseline Data on 2093 Patients","volume":"12","author":"Kingswood","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.pediatrneurol.2014.10.006","article-title":"Pilot Validation of the Tuberous Sclerosis-Associated Neuropsychiatric Disorders (TAND) Checklist","volume":"52","author":"Leclezio","year":"2015","journal-title":"Pediatr. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1177\/08830738040190090601","article-title":"Behavioral and Cognitive Aspects of Tuberous Sclerosis Complex","volume":"19","author":"Prather","year":"2004","journal-title":"J. Child Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S1474-4422(15)00069-1","article-title":"Neurological and Neuropsychiatric Aspects of Tuberous Sclerosis Complex","volume":"14","author":"Curatolo","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Osman, M.F., Hadid, F., Ben Omran, T., Aden, M., Al-Maadid, F., Altaraqji, S., Mohamed, K., and Benini, R. (2025). Neuropsychiatric profile in tuberous sclerosis complex patients with epilepsy. Front. Pediatr., 12.","DOI":"10.3389\/fped.2024.1436061"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1097\/YCO.0000000000000136","article-title":"Advances in the Treatment of Tuberous Sclerosis Complex","volume":"28","author":"Leclezio","year":"2015","journal-title":"Curr. Opin. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s42466-021-00130-3","article-title":"Quality of Life and Its Predictors in Adults with Tuberous Sclerosis Complex (TSC): A Multicentre Cohort Study from Germany","volume":"3","author":"Conradi","year":"2021","journal-title":"Neurol. Res. Pract."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/cns.13473","article-title":"Quality of Life in Children with Tuberous Sclerosis Complex: A Pediatric Cohort Study","volume":"27","author":"Ding","year":"2021","journal-title":"CNS Neurosci. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1056\/NEJMoa1213507","article-title":"Sturge-Weber Syndrome and Port-Wine Stains Caused by Somatic Mutation in GNAQ","volume":"368","author":"Shirley","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1177\/08830738030180080701","article-title":"Pathophysiology of Sturge-Weber Syndrome","volume":"18","author":"Comi","year":"2003","journal-title":"J. Child Neurol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1111\/epi.12342","article-title":"Long-term functional outcomes and their predictors after hemispherectomy in 115 children","volume":"54","author":"Moosa","year":"2013","journal-title":"Epilepsia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.eplepsyres.2018.03.020","article-title":"Spikes might precede seizures and predict epilepsy in children with Sturge-Weber syndrome: A pilot study","volume":"143","author":"Bar","year":"2018","journal-title":"Epilepsy Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1528-1167.2006.00630.x","article-title":"Quantitative EEG Asymmetry Correlates with Clinical Severity in Unilateral Sturge-Weber Syndrome","volume":"48","author":"Hatfield","year":"2007","journal-title":"Epilepsia"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/pde.13304","article-title":"Screening for Sturge-Weber Syndrome: A State of the art Review","volume":"35","author":"Zallmann","year":"2018","journal-title":"Pediatr. Dermatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13023-024-03527-w","article-title":"Multidisciplinary, Multicenter Consensus for the Care of Patients Affected with Sturge-Weber Syndrome","volume":"20","author":"Diociaiuti","year":"2025","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1016\/j.clinph.2009.06.005","article-title":"Use of Quantitative EEG in Infants with Port-Wine Birthmark to Assess for Sturge-Weber Brain Involvement","volume":"120","author":"Ewen","year":"2009","journal-title":"Clin. Neurophysiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1203\/PDR.0b013e3181fcb285","article-title":"Focal White Matter Abnormalities Related to Neurocognitive Dysfunction: An Objective Diffusion Tensor Imaging Study of Children with Sturge\u2013Weber Syndrome","volume":"69","author":"Alkonyi","year":"2011","journal-title":"Pediatr. Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Solomon, C.R., McCann, M., Singh, P., Nemeth, C.L., and Comi, A.M. (2024). Sturge\u2013Weber Syndrome: Updates in Translational Neurology. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1493873"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/ajmg.1320570110","article-title":"Outcome of Sturge-Weber Syndrome in 52 Adults","volume":"57","author":"Sujansky","year":"1995","journal-title":"Am. J. Med. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1177\/088307389501000113","article-title":"Sturge-Weber Syndrome: Age of Onset of Seizures and Glaucoma and the Prognosis for Affected Children","volume":"10","author":"Sujansky","year":"1995","journal-title":"J. Child Neurol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1111\/j.1528-1167.2009.02072.x","article-title":"An Infantile-Onset, Severe, yet Sporadic Seizure Pattern Is Common in Sturge-Weber Syndrome","volume":"50","author":"Kossoff","year":"2009","journal-title":"Epilepsia"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.ejpn.2013.10.003","article-title":"Sturge-Weber Syndrome: From the Past to the Present","volume":"18","author":"Sudarsanam","year":"2014","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.pediatrneurol.2019.04.004","article-title":"Quality of Life in Children with Sturge-Weber Syndrome","volume":"101","author":"Harmon","year":"2019","journal-title":"Pediatr. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yebeh.2018.08.006","article-title":"Autism Spectrum Disorder, Social Communication Difficulties, and Developmental Comorbidities in Sturge-Weber Syndrome","volume":"88","author":"Gittins","year":"2018","journal-title":"Epilepsy Behav."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1007\/s10803-021-05062-0","article-title":"The Prevalence and Profile of Autism in Sturge-Weber Syndrome","volume":"52","author":"Sloneem","year":"2022","journal-title":"J. Autism Dev. Disord."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Stafstrom, C.E., Staedtke, V., and Comi, A.M. (2017). Epilepsy Mechanisms in Neurocutaneous Disorders: Tuberous Sclerosis Complex, Neurofibromatosis Type 1, and Sturge\u2013Weber Syndrome. Front. Neurol., 8.","DOI":"10.3389\/fneur.2017.00087"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1212\/WNL.0000000000002118","article-title":"Behavioral and cognitive outcomes for clinical trials in children with neurofibromatosis type 1","volume":"86","author":"Rietman","year":"2016","journal-title":"Neurology"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Li, Y., Hu, X., Chen, X., Cheng, Y., Jiang, Y., and Wang, X. (2025). Progress in genetic mechanisms and precise treatment of neurocutaneous syndrome-related epilepsy. Front. Neurol., 16.","DOI":"10.3389\/fneur.2025.1642299"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"13141","DOI":"10.1073\/pnas.1004829107","article-title":"Neurofibromin regulates corticostriatal inhibitory networks during working memory performance","volume":"107","author":"Shilyansky","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"dmm049362","DOI":"10.1242\/dmm.049362","article-title":"RAS and beyond: The Many Faces of the Neurofibromatosis Type 1 Protein","volume":"15","author":"Anastasaki","year":"2022","journal-title":"Dis. Model. Mech."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Bergoug, M., Doudeau, M., Godin, F., Mosrin, C., Vall\u00e9e, B., and B\u00e9n\u00e9detti, H. (2020). Neurofibromin Structure, Functions and Regulation. Cells, 9.","DOI":"10.3390\/cells9112365"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/j.cell.2008.09.060","article-title":"Neurofibromin regulation of ERK signaling modulates GABA release and learning","volume":"135","author":"Cui","year":"2008","journal-title":"Cell"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Man, A., Di Scipio, M., Grewal, S., Suk, Y., Trinari, E., Ejaz, R., and Whitney, R. (2024). The Genetics of Tuberous Sclerosis Complex and Related mTORopathies: Current Understanding and Future Directions. Genes, 15.","DOI":"10.3390\/genes15030332"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1038\/s41380-024-02863-4","article-title":"Brain Volumes in Genetic Syndromes Associated with mTOR Dysregulation: A Systematic Review and Meta-Analysis","volume":"30","author":"Payne","year":"2025","journal-title":"Mol. Psychiatry"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1111\/epi.18000","article-title":"Pathogenic MTOR Somatic Variant Causing Focal Cortical Dysplasia Drives Hyperexcitability via Overactivation of Neuronal GluN2C NMDA Receptors","volume":"65","author":"Pineau","year":"2024","journal-title":"Epilepsia"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Boff, M.O., Xavier, F.A.C., Diz, F.M., Gon\u00e7alves, J.B., Ferreira, L.M., Zambeli, J., Pazzin, D.B., Previato, T.T.R., Erwig, H.S., and Gon\u00e7alves, J.I.B. (2025). mTORopathies in Epilepsy and Neurodevelopmental Disorders: The Future of Therapeutics and the Role of Gene Editing. Cells, 14.","DOI":"10.3390\/cells14090662"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s40478-025-02113-w","article-title":"Cell\u2013cell communication dysregulation in tuberous sclerosis complex cortical tubers and focal cortical dysplasia","volume":"13","author":"Scheper","year":"2025","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s10456-022-09841-w","article-title":"A Novel Somatic Mutation in GNAQ in a Capillary Malformation Provides Insight into Molecular Pathogenesis","volume":"25","author":"Galeffi","year":"2022","journal-title":"Angiogenesis"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1182\/hematology.2024000598","article-title":"Molecular Landscape and Classification of Vascular Anomalies","volume":"2024","author":"Seront","year":"2024","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.jid.2023.08.028","article-title":"GNAQ\/GNA11 Mosaicism Causes Aberrant Calcium Signaling Susceptible to Targeted Therapeutics","volume":"144","author":"Zecchin","year":"2024","journal-title":"J. Investig. Dermatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1093\/neuonc\/nov152","article-title":"Differentiating the mTOR Inhibitors Everolimus and Sirolimus in the Treatment of Tuberous Sclerosis Complex","volume":"17","author":"MacKeigan","year":"2015","journal-title":"Neuro Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1002\/ped4.12312","article-title":"Current Role of Surgery for Tuberous Sclerosis Complex-Associated Epilepsy","volume":"6","author":"Specchio","year":"2022","journal-title":"Pediatr. Investig."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e209525","DOI":"10.1212\/WNL.0000000000209525","article-title":"Seizure, Motor, and Cognitive Outcomes after Epilepsy Surgery for Patients with Sturge-Weber Syndrome: Results from a Multicenter Study","volume":"103","author":"Wang","year":"2024","journal-title":"Neurology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1002\/cns3.20070","article-title":"Preventative Treatment of Tuberous Sclerosis Complex with Sirolimus: Phase I Safety and Efficacy Results","volume":"2","author":"Capal","year":"2024","journal-title":"Ann. Child Neurol. Soc."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13023-024-03495-1","article-title":"Long-Term Neuropsychologic Outcome of Pre-Emptive mTOR Inhibitor Treatment in Children with Tuberous Sclerosis Complex (TSC) under 4 Months of Age (PROTECT), a Two-Arm, Randomized, Observer-Blind, Controlled Phase IIb National Multicentre Clinical Trial: Study Protocol","volume":"20","author":"Driedger","year":"2025","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_91","first-page":"CD011538","article-title":"Education Support Services for Improving School Engagement and Academic Performance of Children and Adolescents with a Chronic Health Condition","volume":"2","author":"Barnett","year":"2023","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Panteliadis, C.P., Benjamin, R., and Hagel, C. (2022). Improving Quality of Life in the Neurocutaneous Syndromes. 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