The clinical and genetic diagnostic criteria of 2021 are summarized below:
| MAJOR FEATURES | MINOR FEATURES |
|---|---|
| Hypomelanotic macules (≥3; at least 5mm diameter) | “Confetti” skin lesions |
| Angiofibroma (≥3) or fibrous cephalic plaque | Dental enamel pits (>3) |
| Ungual fibromas (≥2) | Intraoral fibromas (>2) |
| Shagreen patch | Retinal achromatic patch |
| Multiple retinal hamartomas | Multiple renal cysts |
| Multiple cortical tubers and/or radial migration lines | Nonrenal hamartomas |
| Subependymal nodule (≥2) | Sclerotic bone lesions |
| Subependymal giant cell astrocytoma | |
| Cardiac rhabdomyoma | |
| Lymphangioleiomyomatosis (LAM)* | |
| Angiomyolipomas (>2)* | |
| Definite TSC: 2 major features or 1 major feature with 2 minor features. Possible TSC: either 1 major feature or >2 minor features. * a combination of the 2 Major clinical features LAM and angiomyolipomas without other features does not meet criteria for a definite diagnosis. Genetic diagnosis: A pathogenic variant in TSC1 or TSC2 is diagnostic for TSC. Most TSC-causing variants are sequence variants that clearly prevent TSC1 or TSC2 protein production. Some variants compatible with protein production (e.g., some missense changes) are well established as disease-causing. Other variant types should be considered with caution. |
|
Approximately 15% of individuals with TSC have no pathogenic variant, sometimes called a mutation, identified by conventional genetic testing, and a normal result does not exclude TSC or have any effect on the use of Clinical Diagnostic Criteria to diagnose TSC. Clinical genetic testing identifies pathogenic variants in approximately 85% of DNA samples submitted for testing from individuals who have a definite diagnosis of TSC based on accepted diagnostic criteria. For the remaining 15%, there are several explanations for why we may not find a pathogenic variant. One explanation is genetic mosaicism, in which a pathogenic variant in the TSC1 or TSC2 gene is present in some of the individual’s cells but not all of the cells in the body. Another reason we may not find a pathogenic variant is that the genetic mutation may have occurred in sections of the gene that we do not test because we do not understand how changes in these parts of the genes can cause disease.
Reviewed by Ashley Pounders, MSN, FNP-C, Director of Medical Affairs, TSC Alliance, November 2023.