PIK3CA-related overgrowth spectrum (PROS) isn’t just one thing. It’s called a spectrum because it’s a group of rare syndromes. What they have in common is that they involve body parts that grow too much or have an unusual shape. This happens because of changes, or mutations, in a gene called PIK3CA.
Those changes and the overgrowth they cause can happen in many parts of the body, including the skin, blood vessels, bones, fat, and brain. PROS can have a variety of symptoms, depending on which type it is and which parts of the body are affected. Often, these symptoms are visible when a baby is born, so doctors can diagnose a child with a PROS condition at birth. Sometimes, it happens later in childhood.
Understanding PIK3CA and PROS
Changes in the PIK3CA gene cause PROS because of the gene’s regular job in your body. Like many genes, it has instructions for making a certain protein. The PIK3CA protein controls other proteins that act as important signals in your body. Those signals help to make sure that cells grow, divide, move, and die when they should.
When cells don’t have the right PIK3CA instructions, the protein doesn’t do its job the right way. Faulty PIK3CA leads to mistakes in cell growth. When those mistakes cause cells to grow and divide too fast or live too long, it leads to overgrowth or unusual shapes in the parts of the body where it happens.
In people with PROS, unusual growth can happen in some parts of the body but not others. That’s because the mutations that cause PROS usually aren’t in all of your cells, just some of them.
Unlike many other genetic conditions, PROS isn’t passed on from parent to child. So if your child has it, it doesn’t mean that you have it or that your other children will.
Types of PROS
Sometimes, doctors diagnose PROS itself. Other times, they might give a diagnosis of one of the syndromes that fall under PROS, such as:
Fibroadipose hyperplasia. This type causes patchy growths on limbs or other body parts. It happens when fatty or fibrous tissue or blood vessels grow too much. The growths tend to get worse over time and can cause problems with walking and movement.
CLOVES syndrome. This condition’s name is an acronym that describes its symptoms. C stands for congenital, meaning it’s there at birth. L is for lipomatous, or related to fat (most infants with CLOVES have a visible fatty mass). O is for overgrowth. V is for vascular malformations, or unusual blood vessels, which can cause things like birthmarks or prominent veins. E is for epidermal nevus, a kind of skin lesion. S is for spinal or skeletal problems, including a curved spine, called scoliosis. People with CLOVES can have other signs too, such as large hands, feet, fingers, or toes and wide spaces between toes and fingers.
Megalencephaly-capillary malformation (MCAP) syndrome. This form of PROS causes overgrowth of the brain and other body parts, such as blood vessels and parts of the face. People with MCAP syndrome may have a developmental delay and unusual fingers and toes.
Hemihyperplasia-multiple lipomatosis (HHML) syndrome. This type often affects the growth of arms and legs. HHML syndrome causes slow-growing and painless fatty masses under the skin in many parts of the body. These often happen on the back, torso, legs, arms, and fingers. There may also be unusual blood vessels.
Hemimegalencephaly. In this type, all or half of the brain is bigger than usual. There may also be changes in blood vessels. Children with hemimegalencephaly may have seizures, paralysis, and developmental delays.
Facial infiltrating lipomatosis. This disorder includes painless swelling or overgrowth of part of the face. It often happens on only one side of the head. Sometimes, masses grow from nerves, or part of the tongue is bigger than usual. Bones and teeth also may be affected.
There’s no cure for PROS, but there are ways to manage the condition and its symptoms. Your child’s doctor may recommend surgery to remove overgrowths, especially if they’re causing trouble with movement or other activities. Surgery might also relieve pressure on the brain, correct scoliosis, or manage other problems. Medications can help with seizures or other symptoms.
What’s Ahead for My Child?
PROS is a lifelong condition. The overgrowth of tissues may affect your child’s daily life in a number of ways. Since PROS is so variable and can affect different parts of the body, the outlook and symptoms can vary a lot from one person to the next. For example, when the brain is affected, it can lead to developmental delays and learning differences.
Some people with PROS also may be more likely to get cancer. (Changes in the PIK3CA gene also show up in tumors of people with cancer who don’t have PROS.) Ask your doctor about your child’s risk now and in the future.