The prospect of novel orphan therapeutic protocol for TSC2/PKD1 contiguous gene syndrome: a case report
Bogdan D Agavriloaei1,2, Radu C Costache1,2, Ramona G Babici3,4
1Grigore T. Popa University of Medicine and Pharmacy of Iasi, Iasi, 700115, Romania.
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.
Insights
Autosomal dominant polycystic kidney disease and tuberous sclerosis complex rarely co-occur. A TSC2/PKD1 contiguous gene deletion syndrome case highlights diagnostic challenges and a novel therapeutic approach with tolvaptan and everolimus.
Area of Science:
- Genetics
- Nephrology
- Oncology
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) and tuberous sclerosis complex (TSC) are rare inherited multisystemic diseases.
- Large deletions on chromosome 16 can cause TSC2/PKD1 contiguous gene deletion syndrome (PKDTS), posing diagnostic and management difficulties.
Purpose of the Study:
- To report a rare case of TSC2/PKD1 contiguous gene deletion syndrome.
- To investigate an innovative therapeutic strategy for this complex genetic disorder.
Main Methods:
- Clinical assessment of a patient with overlapping ADPKD and TSC features.
- Genetic testing to confirm TSC2/PKD1 contiguous gene deletion syndrome.
- Initiation of tolvaptan for ADPKD and consideration of everolimus for TSC manifestations.
Main Results:
- The patient was diagnosed with TSC2/PKD1 contiguous gene deletion syndrome.
- Tolvaptan treatment was started to slow ADPKD progression.
- Everolimus was considered to manage angiomyolipomas and reduce bleeding risk.
Conclusions:
- Accurate diagnosis requires integrating clinical evaluation with genetic testing for overlapping genetic disorders.
- A combined therapeutic approach using tolvaptan and everolimus shows potential for PKDTS.
- Further research is needed to validate the efficacy and safety of this treatment strategy.
