TSC2/PKD1 Contiguous Gene Deletion Syndrome: A Case Series
Eduardo de Oliveira Valle1, Mateus Coelho Guerreiro1, Jose Otto Reusing2
1Division of Nephrology, School of Medicine, University of São Paulo, São Paulo, Brazil; Division of Molecular Medicine, School of Medicine, University of São Paulo, São Paulo, Brazil.
Summary
TSC2/PKD1 contiguous gene deletion syndrome (CGS) shows a variable clinical course, with some patients reaching end-stage kidney disease (ESKD) later than previously thought. This genetic disorder can present with kidney phenotypes similar to severe autosomal dominant polycystic kidney disease (ADPKD).
Area of Science:
- Genetics and rare diseases
- Nephrology and kidney disease progression
Background:
- TSC2/PKD1 contiguous gene deletion syndrome (CGS) is characterized by features of tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD).
- CGS has been historically associated with a severe kidney phenotype, including childhood-onset end-stage kidney disease (ESKD) within three decades.
- Recent reports suggest a more variable clinical course for CGS, necessitating further characterization.
Purpose of the Study:
- To characterize the clinical spectrum and natural history of TSC2/PKD1 contiguous gene deletion syndrome (CGS).
- To investigate the variability in kidney survival and ESKD progression among CGS patients.
- To compare the kidney phenotype of CGS with severe autosomal dominant polycystic kidney disease (ADPKD).
Main Methods:
- A case series study design was employed.
- Eleven patients and one unaffected individual from two CGS pedigrees were analyzed.
- Clinical data and kidney survival were retrospectively evaluated.
Main Results:
- Patients with CGS exhibited widely variable kidney survival, with some reaching the fourth decade without ESKD, even without mosaicism.
- The median age of ESKD onset was 22.5 years, while individuals not developing ESKD had a median age of 25.5 years.
- The clinical course and age of ESKD onset in CGS patients showed significant variability, overlapping with severe ADPKD phenotypes.
Conclusions:
- Patients with CGS have a more variable clinical course than previously reported, with potential for later ESKD onset, irrespective of mosaicism.
- The kidney phenotype in CGS can range from severe progression to a course resembling severe ADPKD.
- CGS should be considered in patients with severe ADPKD lacking TSC manifestations and in TSC patients with rapidly progressing cystic kidney disease.
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