The prospect of novel orphan therapeutic protocol for TSC2/PKD1 contiguous gene syndrome: a case report

Abstract

Background: Autosomal dominant polycystic kidney disease (ADPKD, OMIM # 601313, # 173900) and tuberous sclerosis complex (TSC2, OMIM # 191092, #613254) are inherited multisystemic diseases that rarely associate. Large deletion on chromosome 16 can result in TSC2/PKD1 contiguous gene (deletion) syndrome (PKDTS, OMIM # 600273) presenting significant diagnostic and management challenges. Case presentation: A 50-year-old male presented clinical features consistent with autosomal dominant polycystic kidney disease (ADPKD) and signs of tuberous sclerosis complex (TSC), such as multiple facial angiofibroma, cortical tubers, cerebral hamartomas, and renal and hepatic angiomyolipomas, was investigated for the multisystemic disease pattern. Genetic testing confirmed the diagnosis of TSC2/PKD1 contiguous gene deletion syndrome (PKDTS), leading to the initiation of tolvaptan treatment to reduce the progression of ADPKD and considering everolimus as a potential therapeutic solution to decrease the size of angiomyolipomas, thereby minimizing the risk of spontaneous bleeding. Our report underlines for the first time, up to our knowledge, that the proposed therapy protocol for PKD1/TSC2 contiguous gene deletion syndrome could have potential. Conclusions: This case illustrates the importance of recognizing overlapping genetic disorders, and providing insights into an innovative therapeutic approach. By integrating detailed clinical assessment with genetic testing, the diagnosis was clarified, and targeted therapies can be selected to address the dual impact of ADPKD and TSC; however, further studies are needed to evaluate the efficacy and safety of this approach. We also emphasize the need to recognize other cases of renal polycystic disease associated with angiomyolipomas and cutaneous manifestations.