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ISSN (Print): 1574-8871
ISSN (Online): 1876-1038

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Case Report

Identification of a Novel TSC2 c.170G>A Missense Variant: A Case Report and Elaboration on the Yield of Targeted Options against Tuberous Sclerosis Complex Manifestations

Author(s): Georgios Papageorgiou*, Nikolaos Skouteris, Christos Valavanis, Gabriela-Monica Stanc, Efthymia Souka and Nikolaos Charalampakis

Volume 18, Issue 4, 2023

Published on: 18 October, 2023

Page: [304 - 312] Pages: 9

DOI: 10.2174/0115748871258042230921052344

Price: $65

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Abstract

Background: Tuberous sclerosis complex (TSC) is a rare genetic disease that affects multiple organs and affects the quality of life. Mutations in TSC1 and TSC2 genes are causing dysregulations in the mammalian target of the rapamycin (mTOR) pathway, inducing mostly benign but also malignant tumors, including renal cell carcinoma (RCC). The diagnosis of TSC, based on established clinical and genetic criteria, is essential for the optimal surveillance and management of patients.

Case Presentation: With the current report, we present the case of two sisters who were consequently diagnosed with early-stage chromophobe-like RCC, possibly familial given their young age. The younger sister also had a previous diagnosis of differentiated thyroid carcinoma, for which she had been treated properly. Genetic testing of both revealed the same heterozygous TSC2 variant that is currently regarded as a variant of unknown significance, while both patients did not fulfill the clinical criteria for the diagnosis of TSC. Owing to these data, we opted to manage and surveil both sisters as TSC patients, while we also considered the specific TSC2 variant to be pathogenic - but of low penetrance - based on clinical judgment and functional analyses. Furthermore, we discussed the implementation of mTOR inhibitors for the treatment of TSC complications.

Conclusion: As novel pathogenic variants of TSC genes are constantly being explored, the identification of TSC variants of unknown significance in combination with absent clinical diagnostic criteria cannot exclude a TSC diagnosis. We support the implementation of clinical judgment in assisting the diagnosis of TSC, as well as the enrollment of patients in clinical trials due to the rarity of the disease.

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Graphical Abstract

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