Pik3ca-Related Overgrowth Spectrum

PIK3CA-related overgrowth spectrum (PROS) is a group of rare disorders that cause overgrowth of parts of the body, due to mutations in the PIK3CA gene. Specific disorders in this spectrum include:

• Fibroadipose hyperplasia (also called fibroadipose overgrowth)
• syndrome">CLOVES syndrome
• Megalencephaly-capillary malformation syndrome (MCAP syndrome)
• Hemihyperplasia‐multiple lipomatosis syndrome (HHML syndrome)
• Hemimegalencephaly
• Facial infiltrating lipomatosis (a congenital disorder that causes overgrowth of one side of the face)

Signs and symptoms of PROS depend on the specific disorder present. Depending on the disorder, they can include having a larger-than-normal brain (megalencephaly), low muscle tone (hypotonia), seizures, intellectual disability, changes in the blood vessels (vascular system), and overgrowth of one area of the body (focal overgrowth) or of multiple areas of the body (segmental overgrowth), with normal growth elsewhere.

PROS is usually caused by somatic mutations in the PIK3CA gene. These changes typically are only present in some cells or some areas of the body (called mosaicism), and are not known to be inherited. Rarely, PROS is caused by a de novo germline mutation, which is present in all cells of the body. The diagnosis of a PROS disorder can be confirmed with genetic testing of the PIK3CA gene. Treatment for a PROS disorder may involve surgical interventions, special education, and speech and physical therapies.