PIK3CA-related overgrowth spectrum (NORD)

PIK3CA-related overgrowth spectrum, or PROS, is a group of disorders caused by mutations in the PIK3CA gene, which plays a role in regulating cell growth and division. As a result, mutations can result in uncontrolled growth of affected tissues.

There are many subtypes of PROS, based on the areas and tissues affected.

CLAPO syndrome involves Capillary malformation, also known as “port wine stain”, in the lower lip, Lymphatic malformation in the face and neck, Asymmetry of the face and limbs, and Partial or generalized Overgrowth of one or more body segments.

CLOVES syndrome involves Congenital Lipomatous Overgrowth resulting in fatty swellings on the trunk and/or overgrowth of arms and/or legs that leads to asymmetric enlargement; Vascular malformations including capillary, venous, and/or lymphatic malformations and/or combinations of all of those; Epidermal nevi, presenting as brown bumpy birthmarks on the skin; and Scoliosis, Skeletal, or Spinal anomalies.

Klippel-Trenaunay Syndrome, or KTS, includes capillary malformation, abnormal veins, and limb overgrowth. People with KTS often have lymphatic malformations as well, so depending on the distribution may have some overlap with CLOVES syndrome.

Diffuse Capillary Malformation with Overgrowth, or DCMO, involves capillary malformation over a large area of the body with accompanying overgrowth, often increased size of an involved limb due to increased muscle and bone, but does not include venous or lymphatic malformation.

Fibro-Adipose Vascular Anomaly, or FAVA, is characterized by the development of a mass of blood vessels and fatty tissue within muscles, which can be painful and reduce mobility.

Fibroadipose Hyperplasia, or FAH, results from overgrowth of connective tissues. In a related disorder, Hemihyperplasia Multiple Lipomatosis Syndrome, or HHML, is characterized by multiple fatty growths, along with hemihyperplasia, which is abnormal enlargement of one limb or one side of the body.

Macrodactyly is isolated enlargement of a digit or digits – fingers or toes, due to overgrowth of bone and soft tissue, which can be painful and reduce mobility or dexterity.