{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:50:19Z","timestamp":1765547419223,"version":"build-2065373602"},"reference-count":63,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"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":["JCM"],"abstract":"<jats:p>Introduction: Tuberous sclerosis complex (TSC) is a rare multisystemic genetic disorder characterized by the formation of benign tumors in various organs, including the central nervous system, skin, kidneys, and heart. The diagnosis is based on well-defined clinical criteria, such as those from Schwartz (2007) updated in 2012 by the International Tuberous Sclerosis Complex Consensus Group. The study aims to investigate the clinical, imaging, and molecular characteristics of patients diagnosed with tuberous sclerosis and to explore the correlation between specific genetic mutations (TSC1 and TSC2 genes) and the severity of clinical manifestations. Material and Methods: This is a retrospective longitudinal study of 13 patients diagnosed with tuberous sclerosis, identified in the records of the Bihor Regional Center for Medical Genetics (BRCMG) within the Bihor County Emergency Clinical Hospital from 1984 to 2024. Clinical, imaging, and molecular features were assessed. Patients were evaluated by a multidisciplinary team, including a geneticist, pediatrician, neurologist, psychiatrist, and psychologist. Clinical and imaging data were retrospectively collected from the congenital malformations and genetic disease records of BRCMG Bihor and statistically analyzed. Results: All patients showed clinical and imaging signs consistent with the diagnosis of tuberous sclerosis. Neurological manifestations were present in 83% of patients, including epilepsy and cognitive delays. Renal lesions were detected in 46% of cases, and dermatological lesions, such as facial angiofibromas, were observed in 69% of patients. Mutational variants identified in the TSC2 gene correlated with a more severe clinical presentation, including severe intellectual disability and treatment-resistant seizures, compared to variants in the TSC1 gene. Conclusions: Our study, although involving a small number of patients, highlights the clinical heterogeneity of tuberous sclerosis and the importance of a multidisciplinary approach in patient management. Early diagnosis and ongoing monitoring are essential to improving the quality of life for patients. Further studies are needed to assess the impact of therapeutic interventions and genetic correlations within the studied population.<\/jats:p>","DOI":"10.3390\/jcm14092974","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T11:47:41Z","timestamp":1745581661000},"page":"2974","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tuberous Sclerosis Complex: A Case Series from a Romanian Genetics Center and a Review of the Literature"],"prefix":"10.3390","volume":"14","author":[{"given":"Aurora Alexandra","family":"Jurca","sequence":"first","affiliation":[{"name":"Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramona","family":"Hodisan","sequence":"additional","affiliation":[{"name":"Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandru Daniel","family":"Jurca","sequence":"additional","affiliation":[{"name":"Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, 020021 Bucure\u0219ti, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanziana","family":"Jurca","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Trandafir","sequence":"additional","affiliation":[{"name":"Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiberia","family":"Ilias","sequence":"additional","affiliation":[{"name":"Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5071-9601","authenticated-orcid":false,"given":"Cosmin","family":"Vesa","sequence":"additional","affiliation":[{"name":"Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia Maria","family":"Jurca","sequence":"additional","affiliation":[{"name":"Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania"},{"name":"Regional Center of Medical Genetics Bihor, County Emergency Clinical Hospital Oradea (Part of ERN ITHACA), 410469 Oradea, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.pediatrneurol.2021.07.011","article-title":"Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations","volume":"123","author":"Northrup","year":"2021","journal-title":"Pediatr Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e9379","DOI":"10.1002\/ccr3.9379","article-title":"Atypical Case of Tuberous Sclerosis with Isolated Neurologic Findings: A Case Report","volume":"12","author":"Devkota","year":"2024","journal-title":"Clin. Case Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e166","DOI":"10.3928\/19382359-20170320-01","article-title":"Tuberous Sclerosis Complex: A Review","volume":"46","author":"Randle","year":"2017","journal-title":"Pediatr. Ann."},{"key":"ref_4","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 Iinternational Tuberous Sclerosis Complex Consensus Conference","volume":"49","author":"Northrup","year":"2013","journal-title":"Pediatr. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Jurca, C.M., Kozma, K., Petchesi, C.D., Zaha, D.C., Magyar, I., Munteanu, M., Faur, L., Jurca, A., Bembea, D., and Severin, E. (2023). Tuberous Sclerosis, Type II Diabetes Mellitus and the PI3K\/AKT\/mTOR Signaling Pathways\u2014Case Report and Literature Review. Genes, 14.","DOI":"10.3390\/genes14020433"},{"key":"ref_6","unstructured":"CNAS (2025, January 18). National Program for Rare Diseases. Available online: https:\/\/cnas.ro\/wp-content\/uploads\/2022\/04\/Programul-national-de-tratament-pentru-boli-rare.pdf."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.pediatrneurol.2012.02.015","article-title":"Emerging Treatments in the Management of Tuberous Sclerosis Complex","volume":"46","author":"Kohrman","year":"2012","journal-title":"Pediatr. Neurol."},{"key":"ref_8","first-page":"4766","article-title":"Hamartin, the Product of the Tuberous Sclerosis 1 (TSC1) Gene, Interacts with Tuberin and Appears to Be Localized to Cytoplasmic Vesicles","volume":"58","author":"Plank","year":"1998","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.1093\/hmg\/6.12.2155","article-title":"SA Molecular Genetic and Phenotypic Analysis Reveals Differences between TSC1 and TSC2 Associated Familial and Sporadic Tuberous Sclerosis","volume":"6","author":"Jones","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jaad.2007.05.004","article-title":"Tuberous Sclerosis Complex: Advances in Diagnosis, Genetics, and Management","volume":"57","author":"Schwartz","year":"2007","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1001\/jamadermatol.2014.938","article-title":"Dermatologic and Dental Aspects of the 2012 International Tuberous Sclerosis Complex Consensus Statements","volume":"150","author":"Teng","year":"2014","journal-title":"JAMA Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1046\/j.1365-4362.1998.00495.x","article-title":"Skin Lesions in Children with Tuberous Sclerosis Complex: Their Prevalence, Natural Course, and Diagnostic Significance: Skin Lesions in Tuberous Sclerosis Complex","volume":"37","author":"Schwartz","year":"1998","journal-title":"Int. J. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1046\/j.1365-2133.1996.d01-923.x","article-title":"The Cutaneous Features of Tuberous Sclerosis: A Population Study","volume":"135","author":"Webb","year":"1996","journal-title":"Br. J. Dermatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/bs.adgen.2018.11.003","article-title":"AR Finding a Cure for Tuberous Sclerosis Complex: From Genetics through to Targeted Drug Therapies","volume":"103","author":"Mceneaney","year":"2019","journal-title":"Adv. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.pediatrneurol.2016.07.003","article-title":"Applying the Lessons of Tuberous Sclerosis: The 2015 Hower Award Lecture","volume":"63","author":"Roach","year":"2016","journal-title":"Pediatr. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1186\/s13023-022-02266-0","article-title":"Perfect Match: mTOR Inhibitors and Tuberous Sclerosis Complex","volume":"17","author":"Luo","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e001493","DOI":"10.1161\/JAHA.114.001493","article-title":"Cardiovascular Manifestations of Tuberous Sclerosis Complex and Summary of the Revised Diagnostic Criteria and Surveillance and Management Recommendations from the International Tuberous Sclerosis Consensus Group","volume":"3","author":"Hinton","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e1146","DOI":"10.1542\/peds.2006-0504","article-title":"Drabik M Clinical and Genotype Studies of Cardiac Tumors in 154 Patients with Tuberous Sclerosis Complex","volume":"118","year":"2006","journal-title":"Pediatrics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e117","DOI":"10.1542\/peds.2010-0192","article-title":"Tuberous Sclerosis Complex: Diagnostic Challenges, Presenting Symptoms, and Commonly Missed Signs","volume":"127","author":"Staley","year":"2011","journal-title":"Pediatrics"},{"key":"ref_20","unstructured":"Rout, P., Zamora, E.A., and Aeddula, N.R. (2025). Tuberous Sclerosis. StatPearls, StatPearls Publishing."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/0002-9149(90)91109-J","article-title":"Natural History of Cardiac Rhabdomyoma in Infancy and Childhood","volume":"66","author":"Smythe","year":"1990","journal-title":"Am. J. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5","DOI":"10.15586\/jkcvhl.2020.131","article-title":"Renal Manifestations of Tuberous Sclerosis Complex","volume":"7","author":"Nair","year":"2020","journal-title":"J. Kidney Cancer VHL"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/B978-0-444-52891-9.00038-5","article-title":"Tuberous Sclerosis","volume":"111","author":"Curatolo","year":"2013","journal-title":"Handb. Clin. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1111\/j.1464-410X.2004.05046.x","article-title":"An Epidemiological Study of Renal Pathology in Tuberous Sclerosis Complex","volume":"94","author":"Noakes","year":"2004","journal-title":"BJU Int."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cox, R.L., Calderon de Anda, F., Mangoubi, T., and Yoshii, A. (2018). Multiple Critical Periods for Rapamycin Treatment to Correct Structural Defects in Tsc-1-Suppressed Brain. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00409"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"bcr2013200711","DOI":"10.1136\/bcr-2013-200711","article-title":"Polycystic Kidney Disease and Chronic Renal Failure in Tuberous Sclerosis","volume":"2013","author":"Dhakal","year":"2013","journal-title":"BMJ Case Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kingswood, J.C., Belousova, E., Benedik, M.P., Carter, T., Cottin, V., Curatolo, P., Dahlin, M., D\u2019Amato, L., Beaure d\u2019Aug\u00e8res, G., and de Vries, P.J. (2020). Renal Manifestations of TuberOus SClerosis Complex: Key Findings from the Final Analysis of the TOSCA Study Focussing Mainly on Renal Angiomyolipomas. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.00972"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1038\/sj.ejhg.5201625","article-title":"Tuberous Sclerosis","volume":"14","author":"Yates","year":"2006","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.jaad.2006.11.019","article-title":"Oral Findings in 58 Adults with Tuberous Sclerosis Complex","volume":"56","author":"Sparling","year":"2007","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/epi4.12286","article-title":"Epilepsy in Tuberous Sclerosis Complex: Findings from the TOSCA Study","volume":"4","author":"Nabbout","year":"2019","journal-title":"Epilepsia Open"},{"key":"ref_31","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":"Jansen","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1111\/epi.13467","article-title":"Systemic Disease Manifestations Associated with Epilepsy in Tuberous Sclerosis Complex","volume":"57","author":"Jeong","year":"2016","journal-title":"Epilepsia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1177\/088307389801300106","article-title":"Frontal Lobe Epilepsy Associated with Tuberous Sclerosis: Electroencephalographic-Magnetic Resonance Image Fusioning","volume":"13","author":"Seri","year":"1998","journal-title":"J. Child. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"100516","DOI":"10.1016\/j.ensci.2024.100516","article-title":"Epileptic Seizures Revealing Tuberous Sclerosis in a Tropical Environment: A Study of 12 Case Series","volume":"36","author":"Diallo","year":"2024","journal-title":"eNeurologicalSc"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/mp.2010.115","article-title":"Gestational Immune Activation and Tsc2 Haploinsufficiency Cooperate to Disrupt Fetal Survival and May Perturb Social Behavior in Adult Mice","volume":"17","author":"Ehninger","year":"2010","journal-title":"Mol. Psychiatr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.pediatrneurol.2014.10.004","article-title":"Tuberous Sclerosis Associated Neuropsychiatric Disorders (TAND) and the TAND Checklist","volume":"52","author":"Vries","year":"2015","journal-title":"Pediatr. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1177\/0883073807309788","article-title":"Characterization of Autism in Young Children with Tuberous Sclerosis Complex","volume":"23","author":"Jeste","year":"2008","journal-title":"J. Child. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/ejhg.2011.241","article-title":"Genotype and Cognitive Phenotype of Patients with Tuberous Sclerosis Complex","volume":"20","author":"Black","year":"2012","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1093\/hmg\/7.6.1053","article-title":"Interaction between Hamartin and Tuberin, the TSC1 and TSC2 Gene Products","volume":"7","author":"Nellist","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1097\/GIM.0b013e31803068c7","article-title":"Genotype\/Phenotype Correlation in 325 Individuals Referred for a Diagnosis of Tuberous Sclerosis Complex in the United States","volume":"9","author":"Au","year":"2007","journal-title":"Genet. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Garcia, A.B., Viola, G.D., Corr\u00eaa, B.D., Fischer, T.D., Pinho, M.C., Rodrigues, G.M., Ashton-Prolla, P., and Rosset, C. (2023). An Overview of Actionable and Potentially Actionable TSC1 and TSC2 Germline Variants in an Online Database. Genet. Mol. Biol., 46.","DOI":"10.1590\/1678-4685-gmb-2023-0132"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Rosset, C., Vairo, F., Bandeira, I.C., Correia, R.L., de Goes, F.V., da Silva, R.T.B., Bueno, L.S.M., de Miranda Gomes, M.C.S., de Campos Reis Galv\u00e3o, H., and Neri, J.I.C.F. (2017). Molecular Analysis of TSC1 and TSC2 Genes and Phenotypic Correlations in Brazilian Families with Tuberous Sclerosis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0185713"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Singh, A.K., Olsen, M.F., Lavik, L.A.S., Vold, T., Drabl\u00f8s, F., and Sjursen, W. (2021). Detecting Copy Number Variation in next Generation Sequencing Data from Diagnostic Gene Panels. BMC Med. Genom., 14.","DOI":"10.1186\/s12920-021-01059-x"},{"key":"ref_44","unstructured":"(2025, January 10). 2012 International TSC Clinical Consensus Conference Recommendations. Available online: https:\/\/www.tscinternational.org\/wp-content\/uploads\/2019\/01\/TSCi-Consensus-Guidelines.pdf."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"29","DOI":"10.2478\/amb-2021-0020","article-title":"Molecular-Genetic Characteristics and Genotype-Phenotype Correlations in Bulgarian Patients with Tuberous Sclerosis Complex","volume":"48","author":"Georgieva","year":"2021","journal-title":"Acta Medica Bulg."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Rosengren, T., Nanhoe, S., de Almeida, L.G.D., Sch\u00f6newolf-Greulich, B., Larsen, L.J., Hey, C.A.B., Dun\u00f8, M., Ek, J., Risom, L., and Nellist, M. (2020). Mutational Analysis of TSC1 and TSC2 in Danish Patients with Tuberous Sclerosis Complex. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-66588-4"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2329048X211012817","DOI":"10.1177\/2329048X211012817","article-title":"The Phenotypic Spectrum of Tuberous Sclerosis Complex: A Canadian Cohort","volume":"8","author":"Alsowat","year":"2021","journal-title":"Child. Neurol. Open"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1086\/316951","article-title":"Mutational Analysis in a Cohort of 224 Tuberous Sclerosis Patients Indicates Increased Severity of TSC2, Compared with TSC1, Disease in Multiple Organs","volume":"68","author":"Dabora","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/sj.ejhg.5201402","article-title":"Mutational Analysis of the TSC1 and TSC2 Genes in a Diagnostic Setting: Genotype-Phenotype Correlations and Comparison of Diagnostic DNA Techniques in Tuberous Sclerosis Complex","volume":"13","author":"Sancak","year":"2005","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.pediatrneurol.2019.03.003","article-title":"Tuberous Sclerosis Complex genotypes and developmental phenotype","volume":"96","author":"Farach","year":"2019","journal-title":"Pediatr. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.eplepsyres.2012.07.007","article-title":"Central TSC2 missense mutations are associated with a reduced risk of infantile spasms","volume":"103","author":"Nellist","year":"2013","journal-title":"Epilepsy Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.yebeh.2007.07.010","article-title":"Psychiatric comorbid conditions in a clinic population of 241 patients with Tuberous Sclerosis Complex","volume":"11","author":"Muzykewicz","year":"2007","journal-title":"Epilepsy Behav."},{"key":"ref_53","first-page":"E1","article-title":"Molecular analysis of TSC2\/PKD1 contiguous gene deletion syndrome","volume":"57","author":"Oyazato","year":"2011","journal-title":"Kobe J. Med. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1007\/s00247-016-3549-3","article-title":"Sclerotic Bone Lesions at Abdominal Magnetic Resonance Imaging in Children with Tuberous Sclerosis Complex","volume":"46","author":"Boronat","year":"2016","journal-title":"Pediatr. Radiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1086\/302381","article-title":"Comprehensive Mutation Analysis of TSC1 and TSC2-and Phenotypic Correlations in 150 Families with Tuberous Sclerosis","volume":"64","author":"Jones","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.ejpn.2018.01.026","article-title":"Screening for TSC1 and TSC2 Mutations Using NGS in Greek Children with Tuberous Sclerosis Syndrome","volume":"22","author":"Papadopoulou","year":"2018","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1212\/01.WNL.0000073272.47681.BB","article-title":"A family with seizures and minor features of Tuberous Sclerosis and a novel TSC2 mutation","volume":"61","author":"Kwiatkowski","year":"2003","journal-title":"Neurology"},{"key":"ref_58","first-page":"463","article-title":"Muscular Dystrophies and Myopathies: The Spectrum of Mutated Genes in the Czech Republic","volume":"91","author":"Mazanec","year":"2016","journal-title":"Clin. Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.celrep.2018.09.039","article-title":"Sensitive Periods for Cerebellar-Mediated Autistic-like Behaviors","volume":"25","author":"Tsai","year":"2018","journal-title":"Cell Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/ajmg.c.31653","article-title":"Healthcare Transition from Childhood to Adulthood in Tuberous Sclerosis Complex","volume":"178","author":"Peron","year":"2018","journal-title":"Am. J. Med. Genet. C Semin. Med. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3805\/eands.13.36","article-title":"Difficulty of Transition to Adult Care in a Patient with Tuberous Sclerosis: A Case Report","volume":"13","author":"Yoshinaga","year":"2021","journal-title":"Epilepsy Seizure"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.yebeh.2019.04.027","article-title":"Experience of Follow-up, Quality of Life, and Transition from Pediatric to Adult Healthcare of Patients with Tuberous Sclerosis Complex","volume":"96","author":"Bar","year":"2019","journal-title":"Epilepsy Behav."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Jansen, A.C., Vanclooster, S., de Vries, P.J., Fladrowski, C., Beaure d\u2019Aug\u00e8res, G., Carter, T., Belousova, E., Benedik, M.P., Cottin, V., and Curatolo, P. (2020). Burden of Illness and Quality of Life in TuberOus SClerosis Complex: Findings from the TOSCA Study. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.00904"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/9\/2974\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:21:55Z","timestamp":1760030515000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/9\/2974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,25]]},"references-count":63,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["jcm14092974"],"URL":"https:\/\/doi.org\/10.3390\/jcm14092974","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2025,4,25]]}}}