PIK3CA-related overgrowth spectrum (PROS) is a rare genetic disorder that causes uncontrollable growth of parts of the body. Its symptoms vary greatly and affect children physically and emotionally.

PROS is a group of rare genetic conditions that result from variations in the PIK3CA gene. This gene produces a protein that helps regulate how cells grow, survive, and divide. Mutations in this gene can cause certain cells to grow uncontrollably, leading to a range of symptoms.

The way PROS shows up can differ greatly from person to personTrusted Source. Some people may experience localized overgrowth, such as enlargement of a limb or another specific body part. Others may have more complex symptoms, including:

  • structural changes in blood vessels
  • neurological (nervous system-related) complications
  • orthopedic (bone-related) issues

Researchers have made significant progress in understanding these conditions and are exploring targeted treatments that might help manage the symptoms more effectively.

Several conditions fall under the PROS umbrella. Each has its own set of symptoms, although some may overlap. Specific PIK3CA gene variants occur only within the cells of the affected areas of the body. Because these variants are not present in all cells, they cause overgrowth in only certain areas, not throughout the body.

CLOVES syndrome

“CLOVES” stands for “congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and spinal/skeletal/scoliosis anomalies.” People with CLOVES syndrome often have symptoms such as:

  • fatty tissue overgrowth in the:
    • back
    • legs
    • axilla (the area where the shoulder joint meets the arm)
    • belly
    • buttocks
  • unusual blood vessel formations
  • spinal issues, including a curving of the spine
  • overgrowth of extremities or unevenly sized extremities
  • a higher susceptibility to blood clots
  • asymmetrical kidney size
  • birthmarks on the skin, such as port-wine stains (reddish skin patches caused by atypical capillaries) or moles

Klippel-Trenaunay syndrome (KTS)

KTS interferes with blood clot development, as well as the development of soft tissue (skin and muscles) and bones.

Symptoms of KTS include:

  • port-wine stains
  • vein issues, such as varicose veins or deep vein malformations
  • bone and soft tissue overgrowth, usually affecting one lower limb and potentially leading to mobility challengesTrusted Source

Megalencephaly-capillary malformation syndrome (MCAP)

MCAP affects many organ systems, including the brain, skin, connective tissues, and blood vessels. It can affect blood vessel development and often leads to:

  • megalencephaly (an enlarged brain), which progresses and can lead to a larger body size after birth
  • widening of the brain’s ventricles (sac-like spaces), which may result in developmental delays
  • capillary malformations that cause distinct skin discolorations
  • neurological complications, including seizures and learning disabilities

Fibroadipose hyperplasia

Fibroadipose hyperplasia is a progressive condition that primarily leads to the overgrowth of fibrous and fatty tissue in patches, often on one limb. This can make the affected limb appear significantly larger than the other and can sometimes result in mobility challenges and discomfort.

A person might have extra fingers or toes at birth, but this condition usually is not visible at first.

Isolated overgrowth

Some people experience overgrowth confined toTrusted Source a specific area, internal organ, tissue, or body part, without additional systemic symptoms.

Each type of PROS is unique, and symptoms can range from mild and manageable to severe and life changing.

Common features include:

  • Overgrowth: One leg or arm may be noticeably larger, or overgrowth may affect the face, torso, or internal organs.
  • Vascular malformations: Atypical blood vessels may cause pain, swelling, or bleeding.
  • Skin changes: The skin may have port-wine stains or other discolorations.
  • Neurological symptoms: Seizures and developmental delays can occur, especially in conditions such as MCAP.
  • Orthopedic issues: Scoliosis or differences in limb length may lead to mobility challenges.

The symptoms usually progress slowly over time, so regular checkups are essential for managing these conditions effectively.

While there is no cure for PROS, various treatments can help manage symptoms and improve quality of life. Key treatment options include:

Surgery

In severe cases, surgery may be necessary to address complications such as overgrowth, blood vessel malformations, or skeletal anomalies. Depending on a person’s specific needs, doctors may recommend surgical interventions such as:

  • debulking procedures to remove excess tissue
  • bone realignment to correct structural issues
  • vascular surgery to manage blood vessel issues

These procedures can help improve function, mobility, and overall quality of life.

Supportive therapies

Various supportive therapies can help people manageTrusted Source the physical and functional challenges associated with PROS.

Physical therapy plays a crucial role in maintaining mobility and reducing discomfort due to overgrowth or orthopedic issues.

Occupational therapy assists both children and adults in adapting daily activities to their abilities and needs.

By incorporating these therapies into a comprehensive treatment plan, people with PROS can develop greater mobility, strength, and independence.

Medications

For people who are experiencing neurological symptoms, a doctor may prescribe antiseizure medications to help control seizures and improve overall stability.

Pain managementTrusted Source is another critical aspect of treatment, especially for people who live with vascular-related pain. A combination of medications and other pain relief strategies can enhance comfort and quality of life.

Genetic counseling

Genetic counseling can provide valuable insights for people and families affected by PROS. Understanding the genetic basisTrusted Source of the condition can help families make informed decisions regarding:

  • treatment options
  • ongoing care
  • family planning

This type of support can also help people navigate the emotional and medical complexities that come with the diagnosis of a genetic condition, offering guidance and reassurance throughout their journey.

With research ongoing and new treatments emerging, there is growing hope that people with PROS will be able to live healthier and more comfortable lives.

A PROS diagnosis can present physical, emotional, and social challenges for children and their families. Here’s what to expect:

Physical challenges

Children with PROS may need regular doctor visits, therapy sessions, and possibly surgeriesTrusted Source to manage their condition. Overgrowth and limb differences can affect mobility and daily activities, sometimes making it difficult to participate in physical activities or maintain independence.

Emotional impact

Visible symptoms and frequent medical treatments can affect a child’s self-esteem and mental healthTrusted Source. Navigating social situations may be challenging, and feelings of isolation or frustration are common.

Support groups and individual counseling can provide emotional support, helping children and their families cope with the unique challenges of PROS.

School and social life

A child’s school may need to implement an individualized education plan (IEP) to accommodate learning or mobility challenges. Teachers and classmates may need education about PROS to foster understanding and inclusivity, which can help reduce the possibility of bullying and social isolation.

Encouraging open communication in the school environment can make a significant difference in a child’s confidence and overall experience.

Impact on families

Managing PROS can be stressful and financially demandingTrusted Source, as it often requires ongoing medical care, therapy, and specialized equipment. Families may benefit from connecting with support organizations and other families who are facing similar challenges. These connections can provide both emotional reassurance and practical advice.

Early intervention and a strong support system are key to helping children thrive while coping with the challenges of PROS.

PROS is a rare, complex condition, but gaining a deeper understanding of it can help families and individuals navigate the challenges with more confidence. PROS presents unique medical, emotional, and social concerns. However, ongoing advancements in research and targeted therapies offer options for better symptom management and improved quality of life.

In order to manage the condition effectively, the following elements are crucial:

  • collaboration with a knowledgeable healthcare team
  • early intervention
  • access to supportive resources

As science continues to uncover new treatment possibilities, people with PROS and their families can look forward to a future with greater medical options and enhanced support systems. Staying informed, advocating for proper care, and connecting with a community of support can make a meaningful difference in the journey with PROS.