PIK3CA-related overgrowth syndrome (PROS) is a collection of related but diverse conditions that lead to the enlargement of various body parts.

Symptoms of PROS typically develop before or shortly after birth, but some people may not have symptoms until early childhood.

Different types of PROS are defined based on the types of tissues they affect and the collection of symptoms they cause.

Virtually any tissue in any body system can be affected, including fat, muscle, bone, blood vessels, or nerves. Limbs or digits may be enlarged, or the trunk, or even the brain. This can lead to a diverse set of symptoms and complications depending on which body systems are affected.

PROS is rare, and parents may have many questions when their child receives the diagnosis.

Learn the answers to some of your most frequently asked questions about PROS and the outlook for children affected by this condition.

The prognosis with PROS varies depending on the type of tissues that are affected, the severity of symptoms, and how these change over time.

In some cases, symptoms may be progressive and get worse over time. Other types of PROS tend to stabilize as children get older.

In some cases, if the overgrowth of various tissues gets worse, it may lead to other complications, such as:

  • mobility problems
  • seizures
  • difficulty completing day-to-day activities

This type of progression may happen slowly or quickly, depending on the type of PROS.

People who have PROS that affects their brain tend to have worse outcomes than someone with another type of PROS. Brain enlargement can lead to severe complications such as seizures, cognitive or developmental delays, or nerve problems.

PROS develops as a result of changes in the PIK3CA gene, which encodes for a protein involved in the regulation of cell growth and survival.

The changes seen in PROS cause this protein to be continuously active, meaning cells grow and divide without regulation. This leads to the characteristic overgrowth seen in people with this condition.

Alterations in PIK3CA have also been seen in cancer cells, which similarly grow and divide rapidly. However, PROS is not a cancer because the affected cells cannot spread to other parts of the body over time. The effects are contained to the tissues that are initially affected, and any tumors that develop, such as fatty tumors, are considered benign.

The cancer-causing changes seen in PIK3CA-associated cancers are different from those observed in PROS. As a result, people with PROS have not been found to have an increased risk of developing PIK3CA-associated cancers as a result of the changes in their PIK3CA genes.

Some cases of Wilms tumor — a rare form of kidney tumor — have been seen in children with PROS, though.

Children with certain types of PROS where these tumors are most common (such as CLOVES syndrome) may undergo regular screening via ultrasound to identify any tumors that develop in a timely manner.

PROS is considered a genetic disorder, but it is not inherited. Changes in the PIK3CA gene aren’t passed down from either parent. They happen due to chance during prenatal development — that is, after fertilization but before birth.

Because these genetic changes happen after development has already started, not all cells in the body carry them. Some cells have an unaltered copy of the gene, whereas others carry the altered form. This results in some tissues being affected and others being unaffected.

Because these gene changes can happen at any point during development — and in any cell — this also results in the diverse spectrum of symptoms associated with various PROS types.

Because PROS develops from de novo (new) genetic changes during development, siblings of people with PROS are no more likely to develop the condition than the general population.

Among people with PROS, the risk of passing these changes on to their future children depends on when the gene change occurred during development and whether it affected their own sex cells (i.e., eggs or sperm).

A genetic counselor can help adults with PROS understand the likelihood of their own children developing PROS and help with family planning if needed.

Historically, it’s been hard to estimate how many people are affected by PROS because of the diversity of symptoms that people have.

A study from 2023 estimated that PROS occurs in less than 1 in 22,313 live births, but it’s not clear whether different populations are affected at different rates.

There’s currently no cure for PROS. Treatment typically involves the management of symptoms, but because symptoms vary from person to person, that means that treatment approaches will vary as well.

Depending on the types of symptoms a person has, a variety of approaches may be used, likely in combination. These include:

  • medications
  • surgery
  • laser ablation
  • use of assistive devices
  • physical, occupational, or speech therapy

In most cases, people with PROS will be managed by a multidisciplinary team of doctors who specialize in the various body systems affected by PROS. A pediatrician with experience with PROS can help to coordinate this care.

Can treatments improve quality of life?

The goal of PROS treatment is often to manage symptoms and reduce their effects on daily living. For instance, surgery or assistive devices may be used to make movement easier, or medications may be prescribed to relieve pain.

In a small 2018 study, treatment with the medication alpelisib (Vijoice), which is used to treat severe symptoms of PROS, was linked to improvements in several bothersome effects from PROS, including:

  • body enlargement
  • scoliosis
  • heart problems

A clinical trial examining the effects of this medication on a variety of other outcomes in PROS, including quality of life, is currently underway.

Additional supportive therapies may be recommended to help with the psychological and social aspects of living with PROS. A mental health professional can help someone cope with the emotional aspects of PROS.

Other professionals can help identify government and nonprofit services to help provide support — such as individualized education plan (IEP) services, disability accommodations, or supplemental security income — to help children and their parents maximize their quality of life.

The effects of PROS on the body and, in turn, daily living are highly variable and differ from person to person.

A team of healthcare professionals can help children with PROS and their loved ones understand the condition in a personalized way, including how it should be treated and what kinds of complications may occur.