Guillaume Canaud, MD, PhD, of Necker-Enfants Malades Hospital – AP-HP, the Paris Descartes University, explains why a biopsy is needed to diagnose PIK3CA-related overgrowth syndrome (PROS). 

PROS is a group of rare congenital disorders that lead to the overgrowth of parts of the body. PROS is caused by gain of function mutations in the PIK3CA gene. Specific PROS disorders include fibroadipose hyperplasia, hemihyperplasia multiple lipomatosis (HHML), CLOVES syndrome, macrodactyly, fibroadipose infiltrating lipomatosis, megalencephaly-capillary malformation (MCAP), and dysplastic megalencephaly (DMEG).) 

As Dr. Canaud explains, using a blood sample will not lead to a diagnosis of PROS. Rather, a biopsy of the body region that is showing the overgrowth is necessary to properly diagnose PROS.  Dr. Canaud also notes that most cases of PROS are present at birth and if a pediatrician observed overgrowth in a newborn or baby, they should be referred to a specialty center. that requires individualized management strategies, ideally led by a multidisciplinary team.

Treatment options for PROS are dependent on the condition and overgrowth but may include surgical (e.g., corrective surgery, lesion debulking, amputation) and/or interventional approaches (such as embolization of vascular malformation) with limited success. Recently, alpelisib was approved to manage patients with PROS. The FDA approval was largely based on real-world evidence from EPIK-P1, a retrospective chart review study led by Dr. Canaud. 

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