Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations

Hope Northrup; Mary E Aronow; E Martina Bebin; John Bissler; Thomas N Darling; Petrus J de Vries; Michael D Frost; Zoë Fuchs; Elizabeth S Gosnell; Nishant Gupta; Anna C Jansen; Sergiusz Jóźwiak; J Chris Kingswood; Timothy K Knilans; Francis X McCormack; Ashley Pounders; Steven L Roberds; David F Rodriguez-Buritica; Jonathan Roth; Julian R Sampson; Steven Sparagana; Elizabeth Anne Thiele; Howard L Weiner; James W Wheless; Alexander J Towbin; Darcy A Krueger; International Tuberous Sclerosis Complex Consensus Group

doi:10.1016/j.pediatrneurol.2021.07.011

Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations

Pediatr Neurol. 2021 Oct:123:50-66. doi: 10.1016/j.pediatrneurol.2021.07.011. Epub 2021 Jul 24.

Authors

Hope Northrup¹, Mary E Aronow², E Martina Bebin³, John Bissler⁴, Thomas N Darling⁵, Petrus J de Vries⁶, Michael D Frost⁷, Zoë Fuchs⁸, Elizabeth S Gosnell⁹, Nishant Gupta¹⁰, Anna C Jansen¹¹, Sergiusz Jóźwiak¹², J Chris Kingswood¹³, Timothy K Knilans¹⁴, Francis X McCormack¹⁰, Ashley Pounders⁸, Steven L Roberds⁸, David F Rodriguez-Buritica¹⁵, Jonathan Roth¹⁶, Julian R Sampson¹⁷, Steven Sparagana¹⁸, Elizabeth Anne Thiele¹⁹, Howard L Weiner²⁰, James W Wheless²¹, Alexander J Towbin²², Darcy A Krueger²³; International Tuberous Sclerosis Complex Consensus Group

Collaborators

International Tuberous Sclerosis Complex Consensus Group:
Nicholas M P Annear, Mary E Aronow, Ute Bartels, E Martina Bebin, Moncef Berhouma, John J Bissler, Klemens Budde, Anna Byars, Harry Chugani, Edward W Cowen, Peter B Crino, Paolo Curatolo, Thomas N Darling, Petrus de Vries, Daniel F Dilling, David W Dunn, Rosmary Ekong, Kevin C Ess, David N Franz, Michael Frost, Zoë D B Fuchs, Elizabeth Gosnell, Lisa Guay-Woodford, Nishant Gupta, Luciana Haddad, Anne Halbert, Adelaide A Hebert, Elizabeth P Henske, Gregory L Holmes, Dena Hook, John Hulbert, Anna Jansen, Simon R Johnson, Sergiusz Jóźwiak, Bryan King, J Christopher Kingswood, Timothy K Knilans, Mary Kay Koenig, Bruce Korf, Darcy A Krueger, David J Kwiatkowski, Francis X McCormack, Joel Moss, David Mowat, Kate Mowrey, Rima Nabbout, Mark D Nellist, Hope Northrup, Finbar O'Callaghan, Uday Patel, Ashley Pounders, E Steve Roach, Steven L Roberds, David Rodriguez-Buritica, Robb Romp, Jonathan Roth, Micaela Rozenberg, Stephen J Ruoss, Mustafa Sahin, Julian Sampson, Joshua A Samuels, Matthias Sauter, Catherine A Smith, Keyomaurs Soltani, Steven Sparagana, Shoba Srivastava, Clare Stuart, Joyce M C Teng, Elizabeth A Thiele, Alexander J Towbin, Andrew Trout, Agnies van Eeghen, Stephanie Vanclooster, Henry Z Wang, Mari Wataya-Kaneda, Howard L Weiner, James W Wheless, Patricia Witman, Tim Wright, Joyce Y Wu, Lisa Young

Affiliations

¹ Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas.
² Retina Service, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts.
³ Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama.
⁴ Department of Pediatrics, University of Tennessee Health Science Center and Le Bonheur Children's Hospital, Memphis, Tennessee.
⁵ Uniformed Services University of the Health Sciences, Bethesda, Maryland.
⁶ Division of Child and Adolescent Psychiatry, University of Cape Town, Cape Town, South Africa.
⁷ Minnesota Epilepsy Group, St. Paul, Minnesota.
⁸ TSC Alliance, Silver Spring, Maryland.
⁹ Department of Pediatrics, University of Cincinnati College of Medicine, and Division of Pediatric Dentistry, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
¹⁰ Division of Pulmonary, Critical Care and Sleep Medicine, University of Cincinnati, Cincinnati, Ohio.
¹¹ Pediatric Neurology Unit, Department of Pediatrics, UZ Brussel, Neurogenetics Research Group, Vrije Universiteit Brussel, Brussels, Belgium.
¹² Department of Pediatric Neurology, Medical University of Warsaw, Warsaw, Poland.
¹³ Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Centre, St Georges University of London, London, UK.
¹⁴ Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio.
¹⁵ Division of Medical Genetics, Department of Pediatrics, McGovern Medical School, University of Texas at Houston Medical Center, Houston, Texas.
¹⁶ Dana Children's Hospital, Tel Aviv Medical Center, Tel Aviv University, Israel.
¹⁷ Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University Medical School, Cardiff, Wales, UK.
¹⁸ Scottish Rite for Children and the University of Texas Southwestern Medical Center, Dallas, Texas.
¹⁹ Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts.
²⁰ Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
²¹ Professor & Chief of Pediatric Neurology, Le Bonheur Chair in Pediatric Neurology, University of Tennessee Health Science Center; Director, Neuroscience Institute & Le Bonheur Comprehensive Epilepsy Program, Co-Director Le Bonheur Tuberous Sclerosis Center of Excellence, Le Bonheur Children's Hospital, Memphis, Tennessee.
²² Cincinnati Children's Hospital, Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, Ohio.
²³ Division of Neurology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio. Electronic address: [email protected].

PMID: 34399110
DOI: 10.1016/j.pediatrneurol.2021.07.011

Abstract

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations.

Methods: Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required.

Results: Only two changes were made to clinical diagnostic criteria reported in 2013: "multiple cortical tubers and/or radial migration lines" replaced the more general term "cortical dysplasias," and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSC-associated neuropsychiatric disorders, and new medication approvals.

Conclusions: Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families.

Keywords: Diagnostic criteria; Practical guidance; Surveillance and management guidelines; Tuberous sclerosis complex (TSC).

MeSH terms

Child
Consensus
Humans
Practice Guidelines as Topic*
Tuberous Sclerosis / diagnosis*
Tuberous Sclerosis / therapy*