Problems with the PIK3CA gene can affect the body in many ways. That’s why there are different conditions in the PIK3CA-related overgrowth spectrum (PROS), each with a unique set of symptoms. The tissue that’s affected, such as skin, bones, fat, brain, or blood vessels, depends on which cells in the body carry the mutation.
This wide range of conditions means a similarly wide range of treatments. There is no cure for PROS, but treatments can ease the symptoms of your child’s specific condition and make it easier to live with.
Medications to Treat Symptoms
Your child may take some kind of medication to help with their symptoms. The medicine they need depends on the type and location of their symptoms.
For instance, children with PROS conditions that affect their brain will often have seizures. Their doctor might prescribe epilepsy medications to help. These drugs usually work best if only a small part of your child’s brain has too much growth.
If your child’s syndrome causes overgrowth of skin cells, they’ll have lesions, skin tags, or other kinds of patchy growths called epidermal nevi. Sometimes, skin creams can help with patches that are discolored or thick and wart-like. If lesions are painful or itchy, a dermatologist might prescribe steroids or antihistamines. These could be either pills or creams.
Anti-inflammatory medications, like aspirin, can also help with pain and inflammation. Some early research shows that this type of medicine could also help make PROS symptoms less severe.
Surgery
It’s common for people with PROS to need surgery, especially if they have growths that make it hard to move around. For example, surgery can help correct problems with your child’s bones, such as the spine problem scoliosis, or legs that are different lengths. If your child has overgrowth in their limbs, it probably involves many layers of tissue. This means your care team will treat the problem in stages, and your child might have several surgeries over time.
If your child has an overgrowth of skin cells, their lesions might be painless, but they can sometimes be red, scaly, and very itchy. For these, skin creams may not be enough. Laser treatment can help reduce lesions, but surgery might be the best option to get rid of them completely.
With severe brain overgrowth, medications may not be enough to stop your child from having seizures. In these cases, surgery can be more successful. It can also help if growths are putting physical pressure on your child’s brain or spinal cord. If just one side of the brain is affected, a neurosurgeon might cut the nerves and tissues that connect one side to the other, or they may even completely remove the affected side of the brain. Over time, the remaining side can then learn to make up for the functions that were lost through the surgery.
If both sides of the brain are affected, this can cause more severe symptoms such as more frequent seizures, delayed development, and problems with vision, speech, swallowing, and muscle control. Although the benefits of surgery are more limited here, studies have shown that it can at least help ease seizures.
Your care team will talk with you about whether surgery is the best option for your child. Any complex surgery carries a risk of complications, so they will help you weigh these risks and benefits for your child.
Gene-Suppressing Drugs
Surgery doesn’t fix the root of the problem. Your child’s gene mutation means the overgrowth of their tissues will keep happening. Extra tissue can grow back, meaning your child will need surgeries again later on. For this reason, researchers are studying other medications that could target the PIK3CA mutations themselves.
Because the symptoms of PROS come from overactive PIK3CA genes, experts think that medications that slow down the gene could counter the effects of the mutations. These gene-suppressing drugs are called inhibitors.
One example is rapamycin, which slows down cell growth and division and already treats other conditions, including cancer. A form of rapamycin called sirolimus can reduce overgrowth in people with PROS, although it can also cause side effects.
A drug called BYL719 (Piqray) directly targets the PI3KCA gene and is also a treatment for people with breast cancer who have PI3KCA mutations. Studies of a small number of people with PROS have shown that BYL719 eases overgrowth without serious side effects.
Alpelisib, another targeted therapy, is a direct inhibitor of PIK3CA. It was approved for treatment of patients 2 years and older with severe PROS symptoms.
Ultimately, learning as much as you can about your child’s specific syndrome can help you form a long-term plan that makes their everyday life better. Your child’s care team will guide you as you decide the treatment path that’s best for your child now and in the future.