Guillaume Canaud, MD, PhD, of Necker-Enfants Malades Hospital – AP-HP, the Paris Descartes University, provides an overview of PIK3CA-related overgrowth syndromes (PROS), a group of rare disorders caused by PIK3CA gene mutations.

PROS is a group of rare congenital disorders that lead to the overgrowth of parts of the body. PROS is caused by mutations in the PIK3CA gene, which are usually somatic and mosaic. Specific PROS disorders include:
• Fibroadipose hyperplasia
• Hemihyperplasia multiple lipomatosis (HHML)
• Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal (CLOVES) syndrome
• Macrodactyly
• Fibroadipose infiltrating lipomatosis
• Megalencephaly-capillary malformation (MCAP)
• Dysplastic megalencephaly (DMEG)

As Dr. Canaud explains, these patients have extremely varied clinical presentations that requires individualized management strategies, ideally led by a multidisciplinary team.

Current treatment modalities include surgical (e.g., corrective surgery, lesion debulking, amputation) and interventional approaches (such as embolization of vascular malformation) or a combination of both. 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.

To learn more about PROS and other rare congenital disorders, visit

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