Differential Diagnosis for TSC1 Mutation and Facial Angiofibromas

Given the mutation TSC1(NM_001406592.1):c.-144+1G>C and the presence of facial angiofibromas without other tumors, the following differential diagnoses are considered:

• Single Most Likely Diagnosis

  • Tuberous Sclerosis Complex (TSC): The mutation in the TSC1 gene, combined with the clinical finding of facial angiofibromas, strongly suggests TSC. TSC is an autosomal dominant disorder characterized by the growth of numerous non-cancerous tumors in many parts of the body and is caused by mutations in either the TSC1 or TSC2 gene. Facial angiofibromas are a common and distinctive feature of TSC.

• Other Likely Diagnoses

  • Multiple Endocrine Neoplasia Type 1 (MEN1): Although less likely, MEN1 can present with angiofibromas similar to those seen in TSC. However, the presence of a TSC1 mutation and the specific type of angiofibromas would make TSC more likely.
  • Neurofibromatosis Type 1 (NF1): NF1 can also present with skin manifestations, but the specific combination of a TSC1 mutation and facial angiofibromas points more towards TSC.

• Do Not Miss Diagnoses

  • Lymphangioleiomyomatosis (LAM): Although LAM is more commonly associated with TSC2 mutations, it's crucial not to miss this diagnosis due to its potential for severe respiratory complications. LAM can occur in patients with TSC1 mutations as well, albeit less commonly.
  • Renal Cell Carcinoma: Part of the TSC spectrum includes an increased risk of renal cell carcinoma. Although extensive testing has found no other tumors, ongoing surveillance is necessary due to the risk associated with TSC.

• Rare Diagnoses

  • Birt-Hogg-Dubé Syndrome (BHD): Characterized by skin fibrofolliculomas, renal tumors, and spontaneous pneumothorax. While it's a rare condition, the skin manifestations could potentially be confused with those of TSC, but the genetic mutation and other clinical features would distinguish TSC.
  • Cowden Syndrome: A rare genetic disorder characterized by multiple hamartomas and an increased risk of certain cancers. While it involves skin lesions, the specific mutation and clinical context provided point more strongly towards TSC.