Abstract
Mosaic overgrowth syndromes (OS) are a proteiform ensemble of rare diseases displaying asymmetric overgrowth involving any tissue type, with degrees of severity ranging from isolated malformation to life-threatening conditions such as pulmonary embolism. Despite discordant clinical presentations, all those syndromes share common genetic anomalies: somatic mutations of genes involved in cell growth and proliferation. The PI3K-AKT-mTOR signaling pathway is one of the most prominent regulators of cell homeostasis, and somatic oncogenic mutations affecting this pathway are responsible for mosaic OS. This review aims to describe the clinical and molecular characteristics of the main OS involving the PI3K-AKT-mTOR pathway, along with the treatments available or under development.
This review summarizes available data regarding OS in scientific articles published in peer-reviewed journals.
OS care requires a multidisciplinary approach relying on clinical and radiological follow-up along with symptomatic treatment. However, no specific treatment has yet shown efficacy in randomized control trials.
Clinical classifications of OS led to frequent misdiagnosis. Moreover, targeted therapies directed at causal mutated proteins are developing in OSs through cancer drugs repositioning, but the evidence of efficacy and tolerance is still lacking for most of them.
The genetic landscape of OS is constantly widening and molecular classifications tend to increase the accuracy of diagnosis, opening opportunities for targeted therapies.
OS are a dynamic, expanding field of research. Studies focusing on the identification of genetic anomalies and their pharmacological inhibition are needed.
