Tuberous Sclerosis Complex (TSC)

Tuberous sclerosis complex is a genetic disorder characterized by the growth of numerous benign tumors in vital organs, such as skin, brain, kidneys among others. Common clinical indications of TSC include, but are not limited to:

Skin

• Patches of white- or light-coloured skin (Hypomelanotic macules)
• Oval-shaped skin lesions (Shagreen patches)
• Skin malformations on the forehead (Forehead plaque)
• Rashes on the face (Facial angiofibroma)
• Skin-colours lesions under or around finger nails (Ungual fibromas)

Kidneys

• Kidney cancer (Renal cell carcinoma)
• Soft tissue tumors (Angiomyolipoma)
• Cysts on or around kidneys (Cystic disease)

Brain

• Brain malformations (Cortical dysplasias and subependymal nodules)
• Brain tumour in astrocytes (Subependymal giant cell astrocytoma)

Heart

• Benign tumors of the heart (Cardiac rhabdomyomas)

Lungs

• Growth of smooth muscle cells in and around the lungs (Lymphangioleiomyomatosis)

Eyes

• Benign malformations in the eye (Retinal hamartoma)
• White- or light-coloured lesions in the eye (Chorioretinal hypopigmented lesions)

Genetics and TSC

Although the diagnosis of TSC is often based on clinical findings, such as those above, TSC is generally caused by mutations in one of the two genes (TSC1 and TSC2). Genetics variants can be identified in 75-90% of individuals who meet the clinical diagnostic criteria for TSC, among which 24% and 66% have pathogenic variants (mutation) in TSC1 and TSC2, respectively.¹

Reasons for Genetic Testing

A definitive diagnosis of TSC can be established using clinical findings alone, as long as minimum requirements are met. For example, a diagnosis can be confirmed if either two major features, such as those described above, are present or the combination of one major feature and more than two minor features. Genetic testing can simplify the diagnostic process, as the presence of one pathogenic variant in either TSC1 or TSC2 is sufficient for diagnosis.¹ 

Further, confirmation of a clinical diagnosis through genetic testing can direct medical management, help predict progression of the disease, and provide essential information related to risk for relatives. In particular, testing is recommended for:

• Individuals with a family history of tuberous sclerosis and presentation of the most common symptoms, including hypomelanotic macules, facial angiofibromas, shagreen patches, cortical dysplasias, subependymal nodules, seizures, kidney cysts, rhabdomyomas and others.
• Individuals without a positive family history, but with symptoms resembling tuberous sclerosis
• Individuals with a negative but suspected family history, in order to perform proper genetic counselling (prenatal analyses are available for families with affected individuals once a causative mutation is identified).

LifeLabs Genetics offers the following Next-Generation Sequencing panels (Sequencing and Copy Number Variant analyses)

• Tuberous Sclerosis Panel: TSC1 and TSC2
• TSC1 and TSC2 are also available in the following panels:
  • Broad and Comprehensive Epilepsy Panels
  • Comprehensive Pulmonary Disease Panel
  • Hereditary Cancer Panel
  • Renal Cancer Panel
  • Syndromic Autism Panel

References

1. Northrup et al. Tuberous Sclerosis Complex. Pagon RA, Adam MP, Ardinger HH, et al., editors. Seattle (WA): University of Washington, Seattle; 1993-2017. Last update July 12, 2018.