Which specialty performs genetic testing for TSC1 (Tuberous Sclerosis Complex)?

Genetic Testing for TSC1: Specialty Coordination

Genetic testing for TSC1 (Tuberous Sclerosis Complex) should be ordered and coordinated by any physician managing TSC patients, but must be accompanied by genetic counseling services before and after testing. 1

Primary Coordinating Specialties

The evidence does not specify a single specialty that exclusively performs TSC1 genetic testing. Instead, the guidelines emphasize a multidisciplinary approach with the following key points:

Who Orders the Testing

• Any clinician managing TSC patients can order genetic testing for TSC1 and TSC2, including neurologists, nephrologists, pediatricians, or geneticists, as genetic diagnosis is recommended for all patients with definite or suspected TSC 1

• Genetic counselors must be involved before and after testing to ensure proper interpretation and family counseling 1

Specialty Involvement Based on Clinical Presentation

• Neurologists often coordinate care given that epilepsy is a leading cause of mortality and brain manifestations are nearly universal 2

• Nephrologists frequently manage TSC patients since kidney disease is the most common cause of death in adults with TSC 2

• Medical geneticists or genetic counselors should be consulted for all patients, particularly for:

  • Variant interpretation and classification following American College of Medical Genetics standards 1
  • Family cascade testing when pathogenic variants are identified 1
  • Counseling about the 1-2% recurrence risk in seemingly sporadic cases due to parental mosaicism 1

Critical Testing Considerations

When Standard Testing is Negative

• High-sensitivity genetic analysis detecting variants at allele frequencies as low as 1% is required if initial testing is negative in patients with definite TSC 1

• Mosaicism is common in 10-15% of TSC patients with no mutation identified by conventional testing, with mosaic allele frequencies sometimes below 2% 1, 3

• Analysis of TSC-related tumor tissue may be necessary when blood/saliva DNA testing is negative, as pathogenic variants may be present exclusively in affected tissues 3

Genetic Counseling Requirements

• Pre- and post-test genetic counseling is mandatory whenever possible 1

• Counseling must address the high degree of intrafamilial variability in disease severity, even among family members with the same mutation 1

• All patients with TSC considering having children require genetic counseling 1

Common Pitfalls

• Variants of unknown significance (VUS) should never be used for clinical decision-making due to potential harm from misinterpretation for both the patient and relatives 1

• Negative genetic testing does not exclude TSC - 10-15% of clinically definite TSC patients have no identifiable mutation, often due to low-level mosaicism 1, 3

• Testing should not be routinely performed in patients with isolated angiomyolipoma without other TSC features 1