What is PIK3CA-related overgrowth spectrum (PROS)?

Presently, there are no known cases of inherited PIK3CA-related overgrowth spectrum (PROS). None of the studies have suggested the parent-to-child transmission of PROS. There are no reports of the condition in siblings of the affected person.

Most PROS cases have a somatic mutation, which is a genetic defect that is not inherited. These mutations occur randomly after fertilization (fusion of egg with sperm) and affect the somatic cells that are cells other than the gametes (egg and sperm). The random mutations result in a mixed population of normal and abnormal cells (mosaicism).

In rare cases, PROS could be associated with mutations in the germ cells or gametes (germline mutations). These germline mutations are not inherited from parents. Rather, they occur on their own in the affected person (de novo mutations). A person with a germline mutation in the PIK3CA gene has a 50 percent likelihood of passing the disease to their child. As already stated, no such cases of inherited PROS have been reported so far.

PIK3CA-related overgrowth spectrum (PROS) can cause various health conditions including:

• Fibroadipose hyperplasia (FH):
  • Also called fibro adipose overgrowth, FH causes a patchy overgrowth of any limb or body part due to excessive growth of fatty or fibrous tissue, with or without excessive blood vessels formation.
  • The condition is generally not identifiable at birth and typically worsens with time.
• CLOVES syndrome:
  • Also called congenital lipomatous overgrowth syndrome, this condition is identifiable right at birth (congenital).
  • It is characterized by the following:
    • abnormal fat distribution due to fatty tissue overgrowth,
    • several birthmarks (epidermal nevi),
    • limb overgrowth, and
    • skeletal, spinal, skin, and kidney abnormalities.
• Megalencephaly-capillary malformation syndrome (MCAP syndrome):
  • Also called macrocephaly-cutis marmorata telangiectatica congenita syndrome (M-CMTC), the condition is characterized by a large brain (megalencephaly) that leads to large head size (macrocephaly).
  • Various abnormal capillaries or tiny blood vessels in the skin cause the appearance of pink to red-colored skin patches.
• Hemihyperplasia-multiple lipomatosis syndrome (HHML syndrome):
  • The condition causes asymmetric, nonprogressive overgrowth of the limbs. 
  • Several fatty or lipomatous masses may develop under the skin throughout the body. This especially affects the back, torso, limbs, underarms, and fingers.
  • These lipomatous masses are typically slow-growing and painless.
  • HHML can increase the risk of certain abdominal cancers.
• Hemimegalencephaly:
  • There is an asymmetric overgrowth of the brain and generally involves one side of the brain.
  • This leads to an asymmetric head coupled with problems, such as seizures and learning difficulties.
• Facial infiltrating lipomatosis:
  • This condition causes overgrowth of one side of the face.
  • There could be fatty masses present, affecting one side of the face usually. 
  • The condition may affect the growth of the tongue, jaw, and teeth.