Biomarkers for Tuberous Sclerosis Complex (BioTuScCom)

Study Purpose

Association of specific mutations (genotype) after sequencing the TSC1 and TSC2 gene with the clinical manifestations (phenotype) of the tuberous sclerosis complex in a cohort of clinically well characterized tuberous sclerosis complex patients. The obtained samples will be used to establish a tandem-MS-based biomarker.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.

An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.

Searching Both is inclusive of interventional and observational studies.

Eligible Ages 2 Years - 50 Years
Gender All
More Inclusion & Exclusion Criteria

INCLUSION CRITERIA - Informed consent is obtained from the participant or from the parent / legal guardian - Participant is aged between 2 and 50 years - Diagnosis of TSC is genetically confirmed by CENTOGENE EXCLUSION CRITERIA - Inability to provide informed consent - Participant is younger than 2 or older than 50 years - Diagnosis of TSC is not genetically confirmed by CENTOGENE

Trial Details

Trial ID:

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Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Centogene AG Rostock
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Arndt Rolfs, MD
Principal Investigator Affiliation Centogene AG Rostock
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Overall Status Recruiting
Countries Georgia

The disease, disorder, syndrome, illness, or injury that is being studied.

Hypomelanotic Macules, Facial Angiofibroma, Shagreen Patches, Ungual Fibromas, Cortical Dysplasia, Cardiac Rhabdomyoma, Lymphangioleiomyomatosis, Renal Angiomyolipoma, Subependymal Giant Cell Astrocytoma
Study Website: View Trial Website
Additional Details

INTRODUCTION Tuberous Sclerosis Complex (TSC) is an autosomal dominant genetic disorder characterized by the growth of numerous tumors in different body parts related to dysregulation of the mechanistic target of rapamycin (mTOR) pathway (DiMario et al., 2015; Orlova and Crino, 2010). The overall incidence of TSC is estimated to be as high as 1 in 6000 to 10,000 live birth (Northrup H. et al 2013). The main aspects of TSC that influence the quality of life are associated with the brain: seizures, developmental delay, intellectual disability, and autism. However, the incidence and severity of the various aspects of TSC can vary widely. CLINICAL PRESENTATION Tuberous sclerosis complex (TSC) should be suspected in individuals with some of the following major and/or minor clinical features of the disease (Fig.1):

  • - Major - Hypomelanotic macules Facial or other angiofibromas Shagreen patches Ungual fibromas Cortical dysplasias, including tubers and cerebral white matter migration lines Cardiac rhabdomyoma Lymphangioleiomyomatosis Multiple retinal nodular hamartomas Renal angiomyolipoma Subependymal giant cell astrocytoma Subependymal nodules Minor Confetti skin lesions (hypopigmented macules scattered over regions of the body) Dental enamel pits Poliosis (circumscribed depigmentation of hair or eyelashes) Intraoral fibromas Non-renal hamartomas Multiple cysts in the liver, pancreas or bone About 90% of people with TSC develop a range of neurodevelopmental, behavioral, psychiatric, and psychosocial difficulties.
The 'TSC‐associated neuropsychiatric disorders' are abbreviated TAND. Behavioral problems most commonly seen include overactivity, impulsivity, and sleeping difficulties. Frequently diagnosed psychiatric disorders in TSC are: autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), anxiety disorder, and depressive disorder. The psychosocial impacts of TSC include low self-esteem and self-efficacy in the individual, and a burden on the family coping with a complex and unpredictable disorder (de Vries et al., 2018). GENETIC BACKGROUND TSC is generally caused by pathogenic variants in the tumor suppressor genes: TSC1 and TSC2. The TSC1 gene coding for hamartin is located on the chromosome 9q34. The TSC2 gene coding for tuberin is located on chromosome 16p13.3. Hamartin and tuberin form a tumor suppressor complex that regulates the activity of rapamycin complex 1 (mTORC1), a cell growth and proliferation regulator (Dibble CC et al., 2012). In TSC the mTOR pathway is hyperactivated leading to tumor growth and epileptogenesis (Krueger et al., 2010). Notably, a pathogenic variant in TSC1 or TSC2 are not identified in 10-15% of patients clinically diagnosed TSC, which might result due to mosaicism (Nellist et al., 2015; Qin et al., 2010). Confirmation of a clinical diagnosis of tuberous sclerosis is performed via TSC1 and TSC2 sequencing. There is no cure for TSC, therefore symptomatic therapy is the best possible choice, including mTOR inhibitors, vigabatrin and other antiepileptic drugs for the seizures, and neurosurgery in cases of life-threatening neurological symptoms The aim of the study is established TSC specific biomarker/s. Such biomarkers aim to facilitate the diagnoses, treatment personalization and monitoring. STUDY OBJECTIVES Primary Objective To identify TSC biomarker/s Secondary Objective To explore the clinical robustness, specificity, and long-term variability of TSC biomarker/s 3 STUDY DESIGN Subjects that meet the eligibility criteria will have a research blood sample drawn at the first visit (V1), which is equivalent to 30 drops of blood (less than 1 mL). This will be applied on a Dried Blood Spot DBS-filtercard, called CentoCard® ( The CentoCard® will be sent to CENTOGENE and analysed genetically and biochemically in their specialized laboratory. Subjects will be invited to see their study doctor for several follow-up visits (V2-V13), every 3 months after enrolment in the study, for a period of 36 months (see Table 1). Each visit will include a physical examination, clinical information documentation, and blood sample collection. Table 1: Overview of study visits (V1-V9) QUARTERLY VISITS TIME BLOOD COLLECTION V1 initiation yes V2 3 months yes V3 6 months yes V4 9 months yes V5 12 months yes V6 15 months yes V7 18 months yes V8 21 months yes V9 24 months yes V10 27 months yes V11 30 months yes V12 33 months yes V13 36 months yes Selection and withdrawal of subjects Inclusion Criteria - Informed consent is obtained from the participant or the parent/ legal guardian - The participant is aged between 2 months and 50 years - The diagnosis of TSC is genetically confirmed by Centogene Exclusion Criteria - Informed consent is not obtained from the participant or the parent/ legal guardian - The participant is younger than 2 months or older than 50 years - The diagnosis of TSC is not genetically confirmed by Centogene

Arms & Interventions


: Observation

Patients with Tuberous Sclerosis Complex (TSC)


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International Sites

Tbilisi State Medical University, Tbilisi, Georgia




Tbilisi State Medical University

Tbilisi, , 0186

Site Contact

Tkemaladze, MD


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