Overgrowth syndromes (OS) are a heterogeneous group of disorders characterized by tissue hypertrophy that can be either localized or generalized, affecting both latitudinal and longitudinal growth. Although these syndromes are considered as rare disorders, their exact prevalence is yet unknown. It is likely to be underestimated owing to the variability of the clinical presentation and the broad phenotypic spectrum of the diseases. For these reasons, we have decided to define OS as an asymmetrical disharmonious overgrowth, including brain overgrowth.

Despite the recent advances in understanding the genetic basis, most of the genes involved in OS are not well characterized. However, it mostly concerns the PIK3CA/AKT/mTOR pathway, implicated in controlling cell growth and proliferation. This project will focus on the most common genes involved in this pathway since these genes are frequently mutated in cancer and a huge number of inhibitors are already available or under development. Importantly, as we recently demonstrated that these drugs can be successfully repositioned or repurposed for monogenic disorders.