Background Facial infiltrating 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 FIL is closely associated with PIK3CA mutations. This study aimed to further identify rare clinical features and underlying molecular variants in patients with FIL. Results Eighteen patients were included in this study, and all patients presented with infiltrating adipose tissues confirmed by magnetic resonance imaging. Macrodactyly, polydactyly, hemimegalencephaly and hemihyperplasia were also observed in patients with FIL. In total, eight different PIK3CA mutations were detected in tissues obtained from sixteen patients, including the missense mutations p.His1047Arg (n = 4), p.Cys420Arg (n = 2), p.Glu453Lys (n = 2), p.Glu542Lys (n = 2), p.Glu418Lys (n = 1), p.Glu545Lys (n = 1), and p.His1047Tyr (n = 1) and the deletion mutation p.Glu110del (n = 3). Furthermore, the GNAQ mutation p.Arg183Gln was detected in the epidermal nevus tissue of one patient. Imaging revealed that several patients carrying hotspot mutations had more severe adipose infiltration and skeletal deformities. Conclusions The abundant clinical presentations and genetic profiles of FIL 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.
Hyperactivation of the PI3K/AKT/mTOR signaling pathway caused by PIK3CA mutations is associated with a category of overgrowth syndromes that are defined as PIK3CA-related overgrowth spectrum (PROS). The clinical features of PROS are highly heterogeneous and usually present as vascular malformations, bone and soft tissue overgrowth, and neurological and visceral abnormalities. Detection of PIK3CA variants is necessary for diagnosis and provides the basis for targeted therapy for PROS. Drugs that inhibit the PI3K pathway offer alternatives to conventional therapies. This article reviews the current knowledge of PROS and summarizes the latest progress in precise treatment, providing new insights into future therapies and research goals.
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