AI Article Synopsis
- Somatic overgrowth disorders are rare conditions characterized by the abnormal enlargement of specific tissues, often related to the activation of the PI3K-AKT-mTOR signaling pathway, which is also implicated in cancer.
- Genetic variations can either enhance or inhibit this pathway, leading to excessive cell growth in particular areas, noted in disorders like CLOVES syndrome and Klippel-Trenaunay syndrome.
- Neurofibromatosis type 1 (NF1) involves faulty regulation of this pathway due to mutations in the NF1 gene, resulting in a range of growth abnormalities that can resemble other PIK3CA-related conditions, prompting a focus on their shared genetic and radiological features.
Article Abstract
Somatic overgrowth disorders comprise a wide range of rare conditions that present with focal enlargement of one or more tissue types. The PI3K-AKT-mTOR pathway is a signalling pathway that induces angiogenesis and cell proliferation, and is one of the most commonly overactivated signalling pathways in cancer. The PI3K-AKT-mTOR pathway can be up-regulated by genetic variants that code for proteins in this pathway, or down-regulated by proteins that inhibit the pathway. Mosaic genetic variations can result in cells that proliferate excessively in specific anatomical locations. The PIK3CA-related overgrowth spectrum (PROS) disorders include CLOVES syndrome, macrodystrophia lipomatosa, and Klippel-Trenaunay syndrome among many. The neurofibromatosis type 1 (NF1) gene encodes neurofibromin which down-regulates the PI3K-AKT-mTOR pathway. Thousands of pathological variants in the NF1 gene have been described which can result in lower-than-normal levels of neurofibromin and therefore up-regulation of the PI3K-AKT-mTOR pathway promoting cellular overgrowth. Somatic overgrowth is a rare presentation in NF1 with a wide range of clinical and radiological presentations. Hypertrophy of all ectodermal and mesodermal elements has been described in NF1 including bone, muscle, fat, nerve, lymphatics, arteries and veins, and skin. The shared signalling pathway for cellular overgrowth means that these radiological appearances can overlap with other conditions in the PIK3CA-related overgrowth spectrum. The aim of this review is to describe the genetic basis for the radiological features of NF1 and in particular compare the appearances of the somatic overgrowth disorders in NF1 with other conditions in the PIK3CA-related overgrowth spectrum.
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