In 2021, the International Tuberous Sclerosis Complex Consensus Group reviewed prevalence and specificity of TSC-associated clinical manifestations and updated the TSC diagnostic criteria published in 2013. Clinical features of TSC and genetic testing provide two ways of obtaining a diagnosis of TSC.
The clinical and genetic diagnostic criteria of 2021 are summarized below:
1. Clinical Criteria
A definite diagnosis of Tuberous Sclerosis will be made when an individual has either: 2 major features; or 1 major feature with 2 minor features.
**A combination of the two major clinical features Lymphangioleiomyomatosis (LAM) and Angiomyolipomas without other features does not meet criteria for a Definite Diagnosis.
A possible diagnosis of Tuberous Sclerosis will be made when an individual has either: 1 major feature; or 1 major and 1 minor feature; or more than 2 minor features.
- Angiofibromas (3 or more) or forehead plaque
- Hypomelanotic macules (3 or more at least 5 mm diameter)
- Ungual fibromas (2 or more)
- Shagreen patch
- Multiple retinal hamartomas
- Multiple cortical tubers and/or radial migration lines. This includes tubers and cerebral white matter radial migration lines.
- Subependymal nodule(s) (2 or more)
- Subependymal giant cell astrocytoma(s)
- Cardiac rhabdomyoma
- Lymphangioleiomyomatosis (LAM)**
- Angiomyolipomas (2 or more)**
- Dental enamel pits (more than 3)
- Intraoral fibromas (2 or more)
- Nonrenal hamartomas
- Retinal achromic patch
- “Confetti” skin lesions
- Multiple renal cysts
- Sclerotic bone lesions
2. Genetic Testing Criteria
- Either a TSC1 or TSC2 pathogenic mutation is sufficient to make a Definite Diagnosis of TSC. A pathogenic mutation is defined as a sequence variant that clearly prevents TSC1 or TSC2 protein production. Additionally, some mutations compatible with protein production (e.g., some missense changes) are well established as disease-causing and as sufficient to make a Definite Diagnosis of TSC. Other variants should be considered with caution.
Help us provide high quality TSC information
We rely on the generosity of donors and fundraisers to publish these information pages and keep them up to date. Please support our work if you can so we can continue to provide life changing information and support to families like Harrison’s. Donate now.