In 2012, the International Tuberous Sclerosis Consensus Conference reviewed prevalence and specificity of TSC-associated clinical manifestations and updated the TSC diagnostic criteria from 1998. Clinical features of TSC continue to be a principal means of diagnosis but include additional clarification and simplification. In addition, TSC may now be diagnosed via genetic testing. The new clinical and genetic diagnostic criteria of 2012 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)
- Ungual fibromas (2 or more)
- Shagreen patch or multiple collagenomas
- Multiple retinal hamartomas
- Cortical dysplasias (more than 3). This includes tubers and cerebral white matter radial migration lines.
- Subependymal nodule(s)
- 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
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.