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Table 1 Diagnostic criteria according to the 2012 International Tuberous Sclerosis Complex Consensus Conference [9]

From: Incidence of tuberous sclerosis and age at first diagnosis: new data and emerging trends from a national, prospective surveillance study

Definite diagnosis: Two major diagnostic criteria or one major with greater than or equal two minor diagnostic criteria or the presence of a TSC1 or TSC2 mutation (of confirmed pathogenicitya)

Possible diagnosis: Either one major diagnostic criteria or greater than or equal two minor diagnostic criteria

Major criteria:

• Cortical dysplasias (incl. tubers and cerebral white matter radial migration lines)

• Subependymal nodules (SEN)

• Subependymal giant cell astrocytoma (SEGA)

• Cardiac rhabdomyoma

• Hypomelanotic macules (≥3, at least 5 mm diameter)

• Angiofibromas (n ≥ 3) or fibrous cephalic plaque

• Ungual fibromas (≥2)

• Shagreen patch

• Angiomyolipomas (≥2) b, c

• Lymphangioleiomyomatosis (LAM) b

• Multiple retinal hamartomas

Minor criteria:

• ´Confetti´ skin lesions

• Dental enamel pits (> 3)

• Intraoral fibromas (≥2)

• Multiple renal cysts

• Retinal achromatic patch

• Nonrenal hamartomas

Genetics:

Identification of either a TSC1 or TSC2 pathogenic mutation in DNA from normal tissuea

  1. (From: Northrup H, Krueger DA, on behalf of the International Tuberous Sclerosis Complex Consensus Group. Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 2013; 49: 243–254. © The authors. License Number 4341381420907)
  2. a Pathogenic mutation: a mutation that clearly inactivates the function of the TSC1 or TSC2 proteins (e.g., out-of-frame indel or nonsense mutation), prevents protein synthesis (e.g., large genomic deletion), or is a missense mutation whose effect on protein function has been established by functional assessment (www.lovd.nl/TSC1, www.lovd/nl/TSC2 and Hoogeveen-Westerveld et al., 2012 and 2013). 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 25% of TSC patients have no 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
  3. b A combination of the two major clinical features (lymphangioleiomyomatosis and angiomyolipomas) without other features does not meet criteria for a definite diagnosis
  4. c Angiomyolipomas might also occur in the liver or other organ systems