Criteria
Updated international tuberous sclerosis complex diagnostic criteria[1]
A. Genetic diagnostic criteria
The identification of either a TSC1 or a TSC2 pathogenic mutation in DNA from normal tissue is sufficient to make a definite diagnosis of TSC regardless of clinical findings. A pathogenic mutation is defined as a mutation that clearly prevents protein synthesis and/or inactivates the function of the TSC1 or TSC2 proteins (e.g., nonsense or frameshift variants, large genomic deletions), or is a missense mutation whose effect on protein function has been established by functional assessment.
Other TSC1 or TSC2 variants whose effect on function is less certain do not meet these criteria, and are not sufficient to make a definite diagnosis of TSC. Note that 10% to 15% of TSC patients have no mutation identified by conventional genetic testing, and failure to identify a pathogenic variant does not exclude a diagnosis of TSC, or have any effect on the use of clinical diagnostic criteria to diagnose TSC.
B. Clinical diagnostic criteria
A definite diagnosis of TSC requires the presence of either 2 major features or 1 major feature with 2 or more minor features.
A possible diagnosis of TSC requires either 1 major feature or 2 or more minor features.
Major features:
Hypomelanotic macules (≥3, at least 5 mm in diameter)
Angiofibromas (≥3) or fibrous cephalic plaque
Ungual fibromas (≥2)
Shagreen patch
Multiple retinal hamartomas
Multiple cortical tubers and/or radial migration lines
Subependymal nodule (≥2)
Subependymal giant cell astrocytoma
Cardiac rhabdomyoma
Lymphangioleiomyomatosis (LAM)*
Angiomyolipomas (≥2).*
Minor features:
Confetti skin lesions
Dental enamel pits (≥3)
Intraoral fibromas (≥2)
Retinal achromic patch
Multiple renal cysts
Nonrenal hamartomas
Sclerotic bone lesions.
* A combination of the 2 major clinical features LAM and angiomyolipomas without other features does not meet criteria for a definitive diagnosis.
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