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.

TSC diagnostic criteria

The clinical and genetic diagnostic criteria of 2021 are summarized below:

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.


Reviewed by Ashley Pounders, MSN, FNP-C, November 2023.

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