Tuberous sclerosis complex (TSC) is highly variable in clinical presentation and findings. Disease manifestations continue to develop over the lifetime of an affected individual. Accurate diagnosis is fundamental to implementation of appropriate medical surveillance and treatment.
Updated Diagnostic Criteria for Tuberous Sclerosis Complex.
A. Genetic diagnostic criteria
The identification of either a TSC1 or TSC2 pathogenic mutation in DNA from normal tissue is sufficient to make a definite diagnosis of tuberous sclerosis complex (TSC). A pathogenic mutation is defined as 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. 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.
B. Clinical diagnostic criteria:
- Hypomelanotic macules (≥3, at least 5 mm diameter)
- Angiofibromas (≥3) or fibrous cephalic plaque
- Ungual fibromas (≥2)
- Shagreen patch
- Multiple retinal hamartomas
- Cortical dysplasias*
- Subependymal nodules
- Subependymal giant cell astrocytoma
- Cardiac rhabdomyoma
- Angiomyolipomas (≥2)†
- Confetti skin lesions
- Dental enamel pits (>3)
- Intraoral fibromas (≥2)
- Retinal achromic patch
- Multiple renal cysts
- Nonrenal hamartomas
Definite diagnosis: two major features or one major feature with ≥2 minor features
Possible diagnosis: one major feature or two or more minor features
*Includes tuber and cerebral white matter radial migration lines.
†A combination of the two major clinical features (lymphangioleiomyomatosis and angiomyolipomas) without other features does not meet the criteria for a definite diagnosis.
- Portocarrero LKL, Quental KN, Samorano LP, Oliveira ZNP, Rivitti-Machado MCDM. Tuberous sclerosis complex: review based on new diagnostic criteria. An Bras Dermatol. 2018 Jun;93(3):323-331. [Medline]
- Jacks SK, Witman PM. Tuberous Sclerosis Complex: An Update for Dermatologists. Pediatr Dermatol. 2015 Sep-Oct;32(5):563-70. [Medline]
- Northrup H, Krueger DA; International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013 Oct;49(4):243-54. [Medline]
Created Sep 05, 2019.