Delineation of Phenotypes and Genotypes of Facial Infiltrating Lipomatosis Associated with PIK3CA Mutations

Abstract Background: Facial infiltrative lipomatosis (FIL) is a rare congenital disorder characterized by unilateral facial swelling, for which surgery is the prevailing therapeutic option. Several studies have shown that the development of the FIL is closely associated with PIK3CA mutations. This study aimed to further identify the rare clinical features as well as the underlying molecular variants in patients with FIL. Results: A series of 18 patients were included in this study, and all patients had presented infiltrative manifestations of adipose tissues confirmed by magnetic resonance imaging. We observed that macrodactyly, polydactyly, hemimegalencephaly and hemihyperplasia could also be seen in patients with FIL. In total, eight different PIK3CA mutations were detected in tissues obtained from sixteen patients, respectively, missense mutation p.His1047Arg (n=4), p.Cys420Arg (n=2), p.Glu453Lys (n=2), p.Glu542Lys (n=2), p.Glu418Lys (n=1), p.Glu545Lys ( n=1), p.His1047Tyr (n=1) and deletion mutation p.Glu110del (n=3). Furthermore, the GNAQ mutation p.Arg183Gln was also detected in the epidermal nevus tissue of one patient. Imaging revealed that several patients carrying hotspot mutations had more severe adipose infiltration and skeletal deformity. Conclusions: The clinical presentation and genetic profile of FIL were abundant, but make it difficult to treat. PIK3CA mutations drive the pathogenesis of FIL, and PIK3CA hotspot mutations may lead to more extensive infiltration of lipomatosis. Understanding the molecular variant profile of FIL will facilitate the application of novel PI3K-targeted inhibitors.