Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum.

摘要: Somatic mutations in the phosphatidylinositol/AKT/mTOR pathway cause segmental overgrowth disorders. Diagnostic descriptors associated with PIK3CA include fibroadipose (FAO), Hemihyperplasia multiple Lipomatosis (HHML), Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, Scoliosis/skeletal and spinal (CLOVES) syndrome, macrodactyly, megalencephaly Megalencephaly-Capillary malformation (MCAP) syndrome. We set out to refine understanding of clinical spectrum natural history these phenotypes, now describe 35 patients somatic mutations. The phenotypic data show that previously described disease entities have considerable overlap, represent a spectrum. While this overlaps Proteus syndrome (sporadic, mosaic, progressive) it can be distinguished by absence cerebriform connective tissue nevi distinct history. malformations were found 15/35 (43%) epidermal 4/35 (11%) patients, lower than Unlike 31/35 (89%) had congenital overgrowth, 35/35 was asymmetric disproportionate. Overgrowth mild little postnatal progression most, while others severe progressive requiring surgeries. Novel findings include: adipose dysregulation present all unilateral is predominantly left-sided, affects extremities more upper progresses distal proximal pattern, most severely affected marked paucity unaffected areas. current are consistent some genotype-phenotype correlation, cannot yet confirmed.