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Tuberous Sclerosis (TS) is a syndrome with multisystemic involvement that has an autosomal dominant origin and involves the TSC1 and TSC2 genes on chromosomes 9 and 16, respectively. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by a mutation mainly in the PKD1 gene on chromosome 16, adjacent to the TSC2 gene, and is characterized by the development of multiple cysts, predominantly in the kidneys.
We report a case of simultaneous involvement of both diseases, suggesting the diagnosis of TSC2/PKD1 Contiguous Gene Syndrome (CGS TSC2/PKD1), which is characterized by the early development of symptoms in multiple systems and a worse prognosis, with a prevalence of 2-3% of patients with TS.
A young male patient was diagnosed with TS at 11 years old through biopsy of skin lesions, with onset of symptoms at 8 months. Referred to a nephrologist due to hyperechoic nodular images in both kidneys on ultrasound of the urinary system, compatible with angiomyolipomas, in addition to several cysts of different sizes and renal scintigraphy with a mild deficit in bilateral renal function. No family history of TS and kidney disease. At the age of 24, he began experiencing seizures, with focal epilepsy of the occipital lobe being identified as a result of neurological involvement from TS, with good control with anticonvulsants. During the annual ultrasound follow-up, a significant increase in the number of renal cysts was noted in subsequent years. At the age of 27, the right kidney was identified on a computed tomography measuring 16cm in the longest axis and the left 15cm, with multiple bilateral cortical renal cysts, the largest measuring around 6.5cm. Given the possibility of ADPKD associated with TS, CGS TSC2/PKD1 was suspected. The patient was referred for genetic monitoring and additional investigation.
Abdominal computed tomography with multiple bilateral renal cysts and infracentimetric angiomyolipomas.
CGS TSC2/PKD1 results from a mutation on chromosome 16, with a synergistic effect due to the involvement of both genes. Faced with a case with characteristic signs and symptoms of ADPKD and early-onset TS, still in childhood, we should suspect CGS TSC2/PKD1, as it may present more severe clinical manifestations and a worse prognosis, with possible rapid progression to chronic kidney disease (CKD). The case highlights the importance of diagnosing this rare entity which, when carried out early, favors genetic counseling and the treatment of CKD.
This case was also presented in the XXII Congresso Paulista de Nefrologia, and re-submiting it is permitted by the organizers of the event.