Tuberous Sclerosis Complex (TSC) is due to TSC1/TSC2 mutations, leading to the development of tumors in multiple organs. Here, we describe an individual with minimal TSC clinical features for whom we identified four different inactivating TSC2 mutations, including two unique mutations in each of angiomyolipoma and angiofibroma tumors; these mutations were not present at all in other analyzed tissues. This suggests that both the angiomyolipoma and angiofibroma occurred by chance, mimicking TSC, but this patient does not have the TSC syndrome. Our case demonstrates the importance of detailed genetic evaluation and appropriate genetic counselling for individuals with marginal TSC features. (By Dr. Katarzyna Klonowska, https://jmg.bmj.com/content/early/2021/10/10/jmedgenet-2021-108160 )

Dr. David Kwiatkowski research group in Brigham and Women’s Hospital/Harvard Medical School