Core Dermatology Diagnoses / CategoriesNeoplastic Benign and Malignant

Tuberous sclerosis

Author: Faculty Reviewers:

Publish date: Posted on
Last updated: October 8, 2021

Keywords #

tuberous sclerosis complex
tuberous sclerosis
hamartomas  

Diagnosis #

Tuberous sclerosis complex (TSC) is a genetic syndrome with multiorgan involvement including brain, skin, kidneys, heart, eyes, and lung. TSC is characterized by hamartomas, or abnormal growth of normal tissues. TSC is associated with mutations in the TSC1 and TSC2 genes, and variable expression leads to different clinical presentations. Identification of the pathogenic genetic mutation is sufficient for the diagnosis of TSC regardless of the clinical presentation.[1,2]

Key Concepts #
  • TSC is a multisystem process that is associated with mutations in the TSC1 and TSC2 genes. 
  • There are major and minor clinical features (see below). 
  • Treatment of dermatologic lesions includes surgical excision, laser, or the use of mTOR-inhibitors such as sirolimus.   
Epidemiology #

The disorder has a birth incidence 1/6000 to 1/10,000 worldwide. Nearly 100% of individuals with TSC have skin or oral findings of the disease.[1] 

Clinical Features #

There are major and minor diagnostic criteria for TSC. A definitive diagnosis of TSC requires the presence of at least 2 major criteria or 1 major and 2 or more minor criteria.  

Major Features: 

  • Multiple angiofibromas or a fibrous cephalic plaque 
  • Multiple Hypomelanotic macules  
  • Ungual fibromas 
  • Shagreen patch 
  • Multiple retinal hamartomas 
  • Cortical dysplasia 
  • Subependymal nodules 
  • Subependymal giant cell astrocytoma 
  • Cardiac rhabdomyoma 
  • Lymphangioleiomyomatosis 
  • Angiomyolipoma  

Minor Criteria: 

  • Dental enamel pits
  • Intraoral fibromas 
  • “Confetti” skin lesions 
  • Nonrenal hamartomas 
  • Multiple renal cysts 
  • Retinal achromic patch 
Differential Diagnoses #
  • Cowden syndrome 
  • Brook-Spiegler syndrome 
  • Birt-Hogg-Dubé syndrome 
Diagnostic Workup #

A diagnosis of TSC can be made clinically but mutations in the TSC1 or TSC2 is diagnostic. A biopsy may be indicated if the clinical diagnosis is uncertain while waiting for genetic studies. 

Treatment #

Bleeding, symptomatic, or disfiguring skin lesions are indications for treatment. Treatment includes surgical excision, laser, or the use of an mTOR inhibitor.  Mammalian target of rapamycin (mTOR) inhibitors such as sirolimus and everolimus are used in the treatment of TSC, as TSC tumors have been associated with an activation of the mTOR pathways.  TSC patients should have annual skin exams.[3,4]  Sun protection is important as hypomelanotic macules are prone to sun damage. Oral lesions should be monitored every 3-6 months. TSC patients have an increased risk of bone cyst formation in the jaw and should undergo a screening panoramic radiographic evaluation at 6 to 7 years of age or earlier for asymmetry, swelling, or delayed tooth eruption. 

References #
  1. Northrup H, Krueger DA. Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. PNU. 2013;49:243-254. doi:10.1016/j.pediatrneurol.2013.08.001
  2. Hinton RB, Prakash A, Romp RL, Krueger DA, Knilans TK. Cardiovascular Manifestations of Tuberous Sclerosis Complex and Summary of the Revised Diagnostic Criteria and Surveillance and Management Recommendations From the International Tuberous Sclerosis Consensus Group. doi:10.1161/JAHA.114.001493
  3. Teng JMC, Cowen EW, Wataya-Kaneda M, et al. Dermatologic and Dental Aspects of the 2012 International Tuberous Sclerosis Complex Consensus Statements. JAMA Dermatology. 2014;150(10):1095. doi:10.1001/jamadermatol.2014.938
  4. Krueger DA, Md HN. Tuberous Sclerosis Complex Surveillance and Management: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. 2013. doi:10.1016/j.pediatrneurol.2013.08.002
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