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Researchers

Natural History Database

Implemented in 2006, the TSC Natural History Database captures clinical data to document the impact of the disease on a person’s health over his or her lifetime. More than 2,000 people with TSC are enrolled in the project among 18 U.S.-based clinical sites. The TSC Alliance provides funding to participating clinics to perform data entry, monitors the integrity of the database, and makes data available to investigators to answer specific research questions and identify potential participants for clinical trials and studies. The TSC Alliance utilizes StudyTRAX as their platform to store and monitor Natural History Data.

Interested in requesting data from the TSC Natural History Database? Please download and fill out this form then email it to Liz Cassidy, MPH, Research Project Manager, at ecassidy@tscalliance.org. All applications will be reviewed by the NHD-BSR Steering Committee.

Participating Institutions

Current sites include:

  1. Boston Children’s Hospital, Boston, MA (Mustafa Sahin, MD, PhD)
  2. Children’s Hospital Colorado, Aurora, CO (Susan Koh, MD) [database only]
  3. Children’s National Medical Center, Washington, DC (William McClintock, MD)
  4. Cincinnati Children’s Hospital Medical Center, Cincinnati, OH (Darcy A. Krueger, MD, PhD)
  5. Cleveland Clinic, Cleveland, OH (Ajay Gupta, MD)
  6. Le Bonheur Children’s Hospital, Memphis, TN (Sarah Weatherspoon, MD)
  7. Loma Linda University Medical Center, Loma Linda, CA (Stephen Ashwal, MD) [database only]
  8. Massachusetts General Hospital, Boston, MA (Elizabeth A. Thiele, MD, PhD)
  9. Minnesota Epilepsy Group, PA, Roseville, MN (Doug Smith, MD)
  10. New York University Langone Medical Center, New York, NY (Josiane LaJoie, MD)
  11. Nicklaus Children’s Hospital, Miami, FL (Paula Schleifer, MD)
  12. Texas Scottish Rite Hospital for Children, Dallas, TX (Steven P Sparagana, MD)
  13. Université de Montréal Sainte-Justine, Montreal, Canada (Philippe Major, MD)
  14. Université de Montréal, Montreal, Canada (Mark Keezer, BA, BSc, MSc, MDCM, PhD)
  15. University of Alabama, Birmingham, AL (Martina Bebin, MD, MPA)
  16. University of California Los Angeles (UCLA), Los Angeles, CA (Rajsekar Rajaraman, MD)
  17. University of Chicago, Chicago, IL (James Tonsgard, MD) [database only]
  18. University of Iowa, Iowa City, IA (Michael Ciliberto, MD)
  19. University of Pennsylvania, Philadelphia, PA (Katherine Nathanson, MD) [database only]
  20. University of Texas Health Science Center, Houston, TX (Hope Northrup, MD)
  21. Washington University, St. Louis, MO (Michael Wong, MD, PhD)
  22. TSC Alliance, Silver Spring, MD (remote consenting and mobile sample collections, Liz Cassidy, MPH)

Circle icons indicate a database only site meaning that biosamples are not collected on site. Pushpins indicate sites approved to collect biosamples on site

Publications

Since 2010, researchers have published fifteen articles in well-regarded, peer-reviewed biomedical journals using data from the TSC Natural History Database. This published research has contributed to our understanding of TSC in a number of relevant fields, including neurology, psychiatry, and ophthalmology. Several papers have found correlations between gene mutations and specific TSC symptoms, as well as correlations between different kinds of symptoms. This type of work is helping us understand why and how different individuals with TSC experience the disease differently.

Please see the TSC Alliance Mendeley group for more information on these papers, as well as other articles produced with the help of TSC Alliance grants, data, and biosamples.

CNS and TAND

  • Parthasarathy S, Mahalingam R, Melchiorre J, Harowitz J, and Devinsky O.  Mortality in tuberous sclerosis complex.  Epilepsy & Behavior 2021 Aug 1, Volume 121, 108032. https://doi.org/10.1016/j.yebeh.2021.108032
    • The authors of this brief communication found that sudden unexpected death in epilepsy (SUDEP) was the leading cause of death in the 31 individuals with TSC whose data they reviewed.   They advise individuals with TSC and their families be counseled about antiseizure medication adherence and lifestyle factors, and the potential role of nighttime supervision or seizure detection devices to prevent SUDEP.
  • Chivukula S, Modiri O, Kashanian A, Babayan D, Ibrahim GM, Well AG, Tu A, Wu JY, Mathern GW, and Fallah A.  Effect of gene mutation on seizures in surgery for tuberous sclerosis complex.  Can J Neurol Sci. 2021 May;48(3):327-334. doi: 10.1017/cjn.2020.185. Epub 2020 Aug 28.
    • This paper focused on outcomes in patients with TSC treated with surgical resection or vagus nerve stimulation.   The authors’ retrospective data review suggested TSC2 mutations result in more severe epilepsy phenotype that is also less responsive to resective surgery.
  • Gupta A, de Bruyn G, Tousseyn S, Krishnan B, Lagae L, Agarwal N, and TSC Natural History Database Consortium.  Epilepsy and neurodevelopmental comorbidities in tuberous sclerosis complex: A natural history study.   Pediatr Neurol. 2020 Feb 4[Online ahead of print] DOI: https://doi.org/10.1016/j.pediatrneurol.2019.12.016
    • This paper concludes that epilepsy remission by appropriate treatment in early life can possibly prevent autism and intellectual disability.
  • Song J, Swallow E, Said Q, Peeples M, Meiselbach M, Signorovitch J, Kohrman M, Korf B, Krueger D, Wong M, Sparagana S. Epilepsy treatment patterns among patients with tuberous sclerosis complex. J Neurol Sci. 2018;391:104-108. doi: 10.1016/j.jns.2018.06.011.
    • The authors found that over 64% of individuals in the database who were prescribed drugs for epilepsy used three or more antiepileptic drugs. Over 22% had epilepsy surgery after trying antiepileptic drugs, and 35% had additional surgery after the first epilepsy surgery.
  • Jeong A, Nakagawa JA, Wong M. Predictors of drug-resistant epilepsy in tuberous sclerosis complex. J Child Neurol. 2017;32(14):1092-1098. doi: 10.1177/0883073817737446.
    • The authors found that children with TSC who had infantile spasms and/or started having focal seizures before one year of age were more likely to have focal seizures that did not respond to antiepileptic drugs.
  • Jeong A, Wong M. Systemic disease manifestations associated with epilepsy in tuberous sclerosis complex. Epilepsia. 2016;57(9):1443-1449. doi: 10.1111/epi.13467.
    • The authors confirmed their hypothesis that systemic disease manifestations such as cardiac rhabdomyomas, renal and skin tumors were associated with the presence of epilepsy or infantile spasms.
  • Kothare SV, Singh K, Hochman T, Chalifoux JR, Staley BA, Weiner HL, Menzer K, Devinsky O. Genotype/phenotype in tuberous sclerosis complex: Associations with clinical and radiologic manifestations. Epilepsia. 2014;55(7):1020-1024. doi: 10.1111/epi.12627.
    • The authors evaluated the associations between the presence of SEGAs and neuropsychiatric disorders in a retrospective review of 916 patients enrolled in the TSC Natural History Database Project.
  • Kothare SV, Singh K, Chalifoux JR, Staley BA, Weiner HL, Menzer K, Devinsky O. Severity of manifestations in tuberous sclerosis complex in relation to genotype. Epilepsia. 2014;55(7):1025-1029. doi: 10.1111/epi.12680.
    • The authors evaluated the association of the TSC1 and TSC2 gene mutations with patient and disease characteristics in a review of clinical data collected from 919 individuals who were enrolled in the TSC Natural History Database.
  • van Eeghen AM, Nellist M, van Eeghen EE, Thiele EA. Central TSC2 missense mutations are associated with a reduced risk of infantile spasms. Epilepsy Res. 2013;103(1):83-87. doi:10.1016/j.eplepsyres.2012.07.007.
    • This paper reports on the analysis of epilepsy and DNA data from the TSC Alliance TSC database and the database of the Carol and James Herscot Center for Children and Adults with Tuberous Sclerosis Complex at Massachusetts General Hospital. The findings suggest that identifying distinct epilepsy characteristics for specific mutation subgroups may help identify relevant biomarkers (indicators), which will assist healthcare providers in making treatment decisions.
  • Ehninger D, Sano Y, de Vries PJ, Dies K, Franz D, Geschwind DH, Kaur M , Lee YS , Li W, Lowe JK, Nakagawa JA, Sahin M, Smith K, Whittemore V, Silva AJ. Gestational immune activation and Tsc2 haploinsufficiency cooperate to disrupt fetal survival and may perturb social behavior in adult mice. Mol Psychiatry. 2012;17(1):62-70. doi: 10.1038/mp.2010.115.
    • This paper (the first to use information from the TSC Natural History Database) raises the possibility that exposure to viral infection may increase the risk of autism spectrum disorder in TSC.

Dermatology

  • Boggarapu S, Roberds SL, Nakagawa JA, Beresford E. Characterization and management of facial angiofibroma related to tuberous sclerosis complex in the United States: retrospective analysis of the natural history database. Orphanet  Journal of Rare Diseases. 2022;17:355. doi: 10.1186/s13023-022-02496-2
    • The authors conducted a retrospective study using data from the TSC Alliance Natural History Database to look at clinical features of TSC specifically in individuals that have facial angiofibromas (FA). The presence of TSC2 mutations and many other TSC-related manifestations were significantly higher in individuals that have FA. Additionally, about one-fourth of individuals in the database were using a topical mTOR inhibitor for FA while ~45% of individuals were not receiving treatment for their FA at the time of publication.
  • Ashley J. Pounders*, Gabrielle V. Rushing*, Sonal Mahida, Bareng Aletta Sanny Nonyane, Emily A. Thomas, and Rabiah Sundus Tameez. Racial differences in the dermatological manifestations of tuberous sclerosis complex and the potential effects on diagnosis and care (2022) Ther Adv Rare Dis 3: 1–16. https://doi.org/10.1177/26330040221140125 *Designates co-first authorship.
    • This publication highlights differences in skin manifestations between races in individuals with TSC and the potential effects of these differences on diagnosis and care. Findings included that Black individuals are less likely to be diagnosed at ⩽1 year of age as compared with White individuals within the NHD. Additionally, the authors found a difference in NHD participation with only 150 Black individuals participating, representing 6% of total NHD participants. Data further indicate a difference between Black and White individuals both in a TSC Center of Excellence and the NHD wherein Black individuals are less likely to receive genetic testing, utilize topical mTOR therapy, and participate in TSC clinical trials.

Ophthalmology

  • Aronow ME, Nakagawa JA, Gupta A, Traboulsi EI, Singh AD. Tuberous sclerosis complex: genotype/phenotype correlation of retinal findings. Ophthalmology. 2012;119(9):1917-1923. doi: 10.1016/j.ophtha.2012.03.020.
    • This paper evaluates the genetic and clinical feature correlations in individuals with astrocytic hamartoma and retinal achromatic patch in TSC.

Tumors

  • Mowrey K, Northrup H, Rougeau P, Hashmi SS, Krueger DA, Ebrahimi-Fakhari D, Towbin AJ, Trout AT, Capal JK, Franz DN, Rodriguez-Buritica D. Frequency, progression, and current management: Report of 16 new cases of nonfunctional pancreatic neuroendocrine tumors in tuberous sclerosis complex and comparison with previous reports. Frontiers in Neurology. 2021;(12):1-11. doi:10.3389/fneur.2021.627672  
    • This paper reports that nonfunctional PNETs occurred at younger ages in the TSC cases reviewed and more commonly compared to previous reports.  Also PNETs in patients treated with systemic mTOR inhibitors had lower rates of growth.

Urology

  • Swallow E, King S, Song J, Peeples M, Signorovitch JE, Liu Z, Prestifilippo J, Frost M, Kohrman M, Korf B, Krueger D, Sparagana S. Patterns of disease monitoring and treatment among patients with tuberous sclerosis complex-related angiomyolipomas. Urology. 2017;0(0). doi: 10.1016/j.urology.2017.02.036.
    • This paper reports that the use of MRIs increased between 2000 and 2012 among patients with TSC-AML. The majority of TSC-AML patients did not receive treatment for angiomyolipoma. Use of nephrectomy decreased over the study period and was particularly rare in patients who initiated an mTOR inhibitor.

Questions?

Contact biosample@tscalliance.org.

Acknowledgments

he TSC Natural History Database and Biosample Repository are governed and wholly funded by the TSC Alliance thanks to generous support from Lorne Waxlax, Bill Watts, the Cowlin Family Fund, the Engles Collaborative Research Fund, Jim and Andrea Maginn, and many additional donors through the Unlock the Cure campaign.

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