Facial infiltrating lipomatosis (FIL) is a congenital disorder caused by the hyperproliferation of adipose and skeletal tissue within the facial region. Infiltration of mature adipose tissue into adjacent structures is a hallmark pathologic finding. In addition to the aesthetic implications, patients may suffer from impaired facial function, including difficulty in swallowing and breathing, sleep disturbances, and visual field displacement. FIL is associated with phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) variants. PIK3CA variants were detected in over 85% of FIL cases, spanning numerous tissue types. Prior research has indicated that PIK3CA hotspot variants may result in a more severe phenotype. However, identical PIK3CA variants can lead to varying degrees of phenotypic severity. This highlights the need for further exploration into the potential contribution of other pathogenic factors. In this study, we reported the co-occurrence of PIK3CA and isocitrate dehydrogenase 1 (IDH1) variants in two patients with FIL and intracranial lesions for the first time. Our study expands the genetic landscape of FIL and provides a view that variants in genes other than PIK3CA may be involved in the pathogenesis of overgrowth disorders.