PIK3CA-related overgrowth syndrome

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1FDA treatments13Active trials4Specialists8Treatment centers1Financial resources

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Overview

PIK3CA-related overgrowth syndrome, often called PROS, is a group of rare conditions caused by changes (mutations) in a gene called PIK3CA. This gene normally helps control how cells grow and divide. When the gene has a mutation, certain cells in the body grow too much, leading to overgrowth of tissues like fat, muscle, bone, or blood vessels in specific parts of the body. The overgrowth can affect almost any area — a limb, the face, the brain, or internal organs — and the pattern is different from person to person. PROS includes several conditions that were previously given separate names, such as CLOVES syndrome, megalencephaly-capillary malformation syndrome (MCAP), Klippel-Trénaunay syndrome, fibroadipose hyperplasia, and hemimegalencephaly, among others. Doctors now group these together under the PROS umbrella because they share the same genetic cause. Symptoms can range from mild to severe depending on which tissues are affected and how many cells carry the mutation. Common features include uneven growth of limbs or body parts, abnormal blood or lymphatic vessels, skin birthmarks, and in some cases brain involvement leading to seizures or developmental delays. Treatment focuses on managing symptoms, and an exciting development is the use of alpelisib (a PIK3CA inhibitor), which has shown real promise in reducing overgrowth in some patients.

Also known as:

Key symptoms:

Overgrowth of one or more limbs, making them larger or longer than the other sideAbnormal fatty tissue growths under the skin or inside the bodyAbnormal blood vessels or lymphatic vessels (vascular malformations)Port-wine stains or other skin birthmarksEnlarged brain or one side of the brain being larger than the otherSeizuresDevelopmental delays or intellectual disability (in cases with brain involvement)Scoliosis or other spine problemsEnlarged or misshapen feet or handsOvergrowth of internal organsLymphatic fluid buildup causing swellingIncreased risk of blood clots

Inheritance

Sporadic

Usually appears on its own, not inherited from a parent

Age of Onset

Neonatal

Begins at or shortly after birth (first 4 weeks)

Orphanet ↗NORD ↗

FDA & Trial Timeline

10 events
Jun 2026Modulatory Effect of Prodigiosin or Pioglitazone on TIME and the Crosstalk to Immune-Checkpoint Protein(s)

Ain Shams University

TrialNOT YET RECRUITING
Nov 2025COMPARE - Pediatric Inflammatory Bowel Disease (PIBD)

University of North Carolina, Chapel Hill

TrialNOT YET RECRUITING
Oct 2025EPIK-P4: A Phase II Single-arm Study to Assess the Efficacy, Safety and Pharmacokinetics of Alpelisib (BYL719) in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum (PROS)

Novartis Pharmaceuticals — PHASE2

TrialRECRUITING
Sep 2025Improving Hypertension Control in Safety-Net Settings: The Boston Hypertension Equity Alliance in Treatment

Boston Medical Center — NA

TrialRECRUITING
Aug 2025The PROmoting Pain Self-Management (PROs) Trial: Holistic Pain Care in the Military Health System

Brooke Army Medical Center — NA

TrialNOT YET RECRUITING
Jul 2025UK ENcorafenib and BInimetinib Real-world Study in Melanoma

Pierre Fabre Ltd

TrialRECRUITING
Jul 2025Use of Airpod Pros as Assistive Technology

The University of Texas at Dallas — NA

TrialRECRUITING
Jun 2025A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children With PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation

Relay Therapeutics, Inc. — PHASE2

TrialRECRUITING
May 2025Implementing REmote SymPtom mOnitoring and maNagement (RESPONd)

University of Calgary — NA

TrialRECRUITING
Sep 2024Innovating Access to Novel Therapies Through Standardized Prospective Integration of Response Evaluations (IMPACT-INSPIRE)

National Cancer Centre, Singapore

TrialRECRUITING

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Treatments

1 available

Vijoice

alpelisib· Novartis Pharmaceuticals CorporationOrphan Drug

treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-Related Overgrowth Spectrum (PROS) who require systemic therapy

Clinical Trials

13 recruitingView all trials with filters →
Phase 25 trials
EPIK-P4: A Phase II Single-arm Study to Assess the Efficacy, Safety and Pharmacokinetics of Alpelisib (BYL719) in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum (PROS)
Phase 2
Actively Recruiting
PI: Novartis Pharmaceuticals (Novartis Pharmaceuticals) · Sites: St Louis, Missouri; Sydney, New South Wales +20 more · Age: 2100 yrs
Study Assessing Long-term Safety and Efficacy of Alpelisib in Patients With PIK3CA-Related Overgrowth Spectrum (PROS) Who Previously Participated in Study CBYL719F12002 (EPIK-P1)
Phase 2
Active
PI: Novartis Pharmaceuticals (Novartis Pharmaceuticals) · Sites: Boston, Massachusetts; Dijon +4 more · Age: 2100 yrs
Improving Theempowerment in Patients With Severe Breast Fibrosis Radio-induced Treated by Pravastatin : Benefit of e-PROs (Electronic " Patient Reported Outcome ") on Breast-related Quality of Life
Phase 2
Actively Recruiting
· Sites: Montpellier · Age: 1899 yrs
A Phase 2 Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, in Adults and Children With PIK3CA Related Overgrowth Spectrum and Malformations Driven by PIK3CA Mutation
Phase 2
Actively Recruiting
· Sites: Phoenix, Arizona; Little Rock, Arkansas +23 more · Age: 299 yrs
Study Assessing the Efficacy, Safety and PK of Alpelisib (BYL719) in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum
Phase 2
Active
PI: Novartis Pharmaceuticals (Novartis Pharmaceuticals) · Sites: San Francisco, California; Aurora, Colorado +34 more · Age: 0100 yrs
N/A1 trial
Use of Airpod Pros as Assistive Technology
N/A
Actively Recruiting
PI: Linda Thibodeau, Ph.D. (The University of Texas at Dallas) · Sites: Richardson, Texas · Age: 1860 yrs
Other6 trials
Lymphedema Specific PROs for Risk Assessment, Prevention and Early Detection
Active
PI: Eli Avisar, MD (University of Miami) · Sites: Miami, Florida · Age: 1899 yrs
Digitally Captured Activity Data and PROs to Monitor Physical Function in Prostate Cancer Patients
Active
PI: Gillian Gresham, PhD (Cedars-Sinai Medical Center) · Sites: Los Angeles, California · Age: 1899 yrs
Patient Reported Outcomes (PROs) in Anal Cancer Patient Treated by Intensity Modulated Radiotherapy (IMRT).
Actively Recruiting
PI: Stefania Manfrida (Fondazione Policlinico Universitario A. Gemelli, I) · Sites: Rome, Lazio · Age: 1899 yrs
PROs Following Low-dose Irradiation for Osteoarthritis
Active
PI: Theodore Yanagihara, MD, PhD (University of North Carolina, Chapel Hill) · Sites: Chapel Hill, North Carolina · Age: 5599 yrs
Enhanced Clinical Decisions for Management of Benign Prostatic Hyperplasia Using Patient-Reported Outcomes
Actively Recruiting
PI: James W. Griffith, PhD (University of Chicago) · Sites: Glenview, Illinois · Age: 5099 yrs
Innovating Access to Novel Therapies Through Standardized Prospective Integration of Response Evaluations (IMPACT-INSPIRE)
Actively Recruiting
PI: Daniel SW Tan, BSc(Hons), MBBS, MRCP, PhD (National Cancer Centre, Singapore) · Sites: Singapore · Age: 2199 yrs

Specialists

4 foundView all specialists →
LM
Leslie G Biesecker, M.D.
BETHESDA, MD
Specialist
PI on 8 active trials
GM
Guillaume Canaud, MD,PHD
Specialist
PI on 1 active trial
JG
James W. Griffith
Specialist
PI on 1 active trial

Treatment Centers

8 centers
🏥 NORD

Baylor College of Medicine Rare Disease Center

Baylor College of Medicine

📍 Houston, TX

🏥 NORD

Stanford Medicine Rare Disease Center

Stanford Medicine

📍 Stanford, CA

🔬 UDN

NIH Clinical Center Undiagnosed Diseases Program

National Institutes of Health

📍 Bethesda, MD

🔬 UDN

UCLA UDN Clinical Site

UCLA Health

📍 Los Angeles, CA

🔬 UDN

Baylor College of Medicine UDN Clinical Site

Baylor College of Medicine

📍 Houston, TX

🔬 UDN

Harvard/MGH UDN Clinical Site

Massachusetts General Hospital

📍 Boston, MA

🏥 NORD

Mayo Clinic Center for Individualized Medicine

Mayo Clinic

📍 Rochester, MN

👤 Mayo Clinic Center for Individualized Medicine

🏥 NORD

UCLA Rare Disease Day Program

UCLA Health

📍 Los Angeles, CA

Financial Resources

1 resources
Vijoice(alpelisib)Novartis Pharmaceuticals Corporation

Travel Grants

No travel grants are currently matched to PIK3CA-related overgrowth syndrome.

Search all travel grants →NORD Financial Assistance ↗

Community

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Latest news about PIK3CA-related overgrowth syndrome

Disease timeline:

New recruiting trial: Use of Airpod Pros as Assistive Technology

A new clinical trial is recruiting patients for PIK3CA-related overgrowth syndrome

New recruiting trial: Patient Reported Outcomes (PROs) in Anal Cancer Patient Treated by Intensity Modulated Radiotherapy (IMRT).

A new clinical trial is recruiting patients for PIK3CA-related overgrowth syndrome

New recruiting trial: Enhanced Clinical Decisions for Management of Benign Prostatic Hyperplasia Using Patient-Reported Outcomes

A new clinical trial is recruiting patients for PIK3CA-related overgrowth syndrome

New recruiting trial: Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CYH33 in Patients With PIK3CA-related Overgrowth Spectrum (PROS) and PIK3CA-related Vascular Malformations (PRVM)

A new clinical trial is recruiting patients for PIK3CA-related overgrowth syndrome

New recruiting trial: Innovating Access to Novel Therapies Through Standardized Prospective Integration of Response Evaluations (IMPACT-INSPIRE)

A new clinical trial is recruiting patients for PIK3CA-related overgrowth syndrome

New recruiting trial: Improving Hypertension Control in Safety-Net Settings: The Boston Hypertension Equity Alliance in Treatment

A new clinical trial is recruiting patients for PIK3CA-related overgrowth syndrome

New recruiting trial: A LONGITUDINAL OBSERVATIONAL STUDY to EVALUATE the EFFICACY of MOVEMENT and IMPLEMENT CONCRETE MOVEMENT RECOMMENDATIONS with the HELP of MOBILITY TRACKING with SMARTWATCHES in SUBJECTS with AXIAL SPONDYLOARTHRITIS

A new clinical trial is recruiting patients for PIK3CA-related overgrowth syndrome

New recruiting trial: PROM Project Urology

A new clinical trial is recruiting patients for PIK3CA-related overgrowth syndrome

New recruiting trial: UK ENcorafenib and BInimetinib Real-world Study in Melanoma

A new clinical trial is recruiting patients for PIK3CA-related overgrowth syndrome

New recruiting trial: EPIK-P4: A Phase II Single-arm Study to Assess the Efficacy, Safety and Pharmacokinetics of Alpelisib (BYL719) in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum (PROS)

A new clinical trial is recruiting patients for PIK3CA-related overgrowth syndrome

Caregiver Resources

NORD Caregiver Resources

Support, advocacy, and financial assistance for caregivers of rare disease patients.

Mental Health Support

Rare disease caregiving can be isolating. Connect with counseling and peer support.

Family & Caregiver Grants

Financial assistance programs specifically for caregivers of rare disease patients.

Social Security Disability

Learn how rare disease patients may qualify for SSDI/SSI benefits.

Questions for your doctor

Bring these to your next appointment

  • Q1.Which tissues or organs are affected in my (or my child's) case, and how will this be monitored over time?,Is alpelisib (Vijoice) appropriate for my situation, and what are the expected benefits and risks?,What type of genetic testing do you recommend, and should it be done on blood or affected tissue?,What specialists should be part of my care team, and how often should I see each one?,Are there clinical trials I should know about for PROS?,What warning signs should prompt me to seek emergency care?,What support services — such as physical therapy, educational support, or mental health resources — are available to us?

Common questions about PIK3CA-related overgrowth syndrome

What is PIK3CA-related overgrowth syndrome?

PIK3CA-related overgrowth syndrome, often called PROS, is a group of rare conditions caused by changes (mutations) in a gene called PIK3CA. This gene normally helps control how cells grow and divide. When the gene has a mutation, certain cells in the body grow too much, leading to overgrowth of tissues like fat, muscle, bone, or blood vessels in specific parts of the body. The overgrowth can affect almost any area — a limb, the face, the brain, or internal organs — and the pattern is different from person to person. PROS includes several conditions that were previously given separate names, s

How is PIK3CA-related overgrowth syndrome inherited?

PIK3CA-related overgrowth syndrome follows a sporadic inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.

At what age does PIK3CA-related overgrowth syndrome typically begin?

Typical onset of PIK3CA-related overgrowth syndrome is neonatal. Age of onset can vary across affected individuals.

Are there clinical trials for PIK3CA-related overgrowth syndrome?

Yes — 13 recruiting clinical trials are currently listed for PIK3CA-related overgrowth syndrome on UniteRare. See the clinical trials section on this page for phase, sponsor, and site details sourced from ClinicalTrials.gov.

Which specialists treat PIK3CA-related overgrowth syndrome?

4 specialists and care centers treating PIK3CA-related overgrowth syndrome are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.

What treatment and support options exist for PIK3CA-related overgrowth syndrome?

1 patient support program are currently tracked on UniteRare for PIK3CA-related overgrowth syndrome. See the treatments and support programs sections for copay assistance, eligibility, and contact details.