| Genetic diagnostic criteria |
| The identificati on of a pathogenic variant in TSC1 or TSC2 in DNA from normal tissue is sufficient to make a definite diagnosis of TSC. A pathogenic variant is defined as a variant that clearly inactivates the function of the TSC1 or TSC2 proteins (eg, nonsense mutation that creates a premature stop codon), prevents protein synthesis (eg, large deletion), or affects protein function, as established by functional assessment (eg, missense mutation that alters the amino acid sequence). |
| Negative genetic testing does not exclude TSC, as conventional genetic testing fails to identify a pathogenic variant in TSC1 or TSC2 in 10 to 25% of patients with TSC. |
| Clinical diagnostic criteria |
| Major clinical features: |
| Hypomelanotic macules (≥3, at least 5 mm diameter) |
| Angiofibromas (≥3) or fibrous cephalic plaque |
| Ungual fibromas (≥2) |
| Shagreen patch (connective tissue nevus) |
| Multiple retinal hamartomas |
| Cortical dysplasias (includes tubers and cerebral white matter radial migration lines) |
| Subependymal nodules |
| Subependymal giant cell astrocytoma |
| Cardiac rhabdomyoma |
| Lymphangioleiomyomatosis (LAM)* |
| Angiomyolipomas (≥2)* |
| Minor clinical features: |
| "Confetti" skin lesions (1 to 2 mm hypomelanotic macules) |
| Dental enamel pits (≥3) |
| Intraoral fibromas (≥2) |
| Retinal achromic patch |
| Multiple renal cysts |
| Nonrenal hamartomas |
| Sclerotic bone lesions |
| Definite TSC: |
| Two major clinical features, or one major and two or more minor clinical features |
| Possible TSC: |
| Either one major clinical feature or two or more minor clinical features |
TSC: tuberous sclerosis complex.
* A combination of LAM and angiomyolipomas without other features does not meet criteria for a definite diagnosis.For most recent version of diagnostic criteria, please refer to: Northrup H, Aronow ME, Bebin EM, et al. Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations. Pediatr Neurol 2021; 123:50.
Original figure modified for this publication. Northrup H, Krueger DA, International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 international tuberous sclerosis complex consensus conference. Pediatr Neurol 2013; 49:243. Table used with the permission of Elsevier Inc. All rights reserved.