Medical Genetics · Segmental Progressive Overgrowth with Fibroadipose Hyperplasia

Treatment Options & Standard of Care

At a Glance

Treatment for segmental progressive overgrowth with fibroadipose hyperplasia is individualized: alpelisib may reduce severe overgrowth, while surgery, orthopedic procedures, or sclerotherapy target specific functional problems. A specialist team monitors benefits and risks.

Managing Segmental Progressive Overgrowth with Fibroadipose Hyperplasia requires a long-term, coordinated strategy rather than a single “fix.” Because the condition affects multiple systems—skin, fat, bone, and blood vessels—care is most effective when managed by a multidisciplinary vascular anomalies team ^[1]^[2]. This team typically includes specialists in genetics, hematology/oncology, interventional radiology, and orthopedic surgery ^[3].

Targeted Medical Therapy: Alpelisib

The landscape of treatment changed significantly when the FDA granted accelerated approval to alpelisib (brand name Vijoice) for adults and children aged 2 years or older with severe manifestations of PROS requiring systemic therapy ^[4].

Unlike traditional medications that only treat symptoms, alpelisib is a PI3K inhibitor—it inhibits the downstream PI3K-alpha signaling pathway driven by the PIK3CA mutation ^[5].

Expected Benefits: In a defining clinical study (EPIK-P1), approximately 27% of patients met a specific trial endpoint of at least a 20% reduction in the volume of prespecified target lesions at 24 weeks ^[4]^[6]. Beyond size reduction, some families report improvements in pain, mobility, and overall quality of life, though eligibility, response, and duration remain individualized ^[7]^[8].
Common and Serious Side Effects: The most frequent side effects include diarrhea, stomatitis (painful mouth sores), and hyperglycemia (high blood sugar) ^[4]^[9]. Additional serious safety concerns include severe cutaneous adverse reactions or rash, hypersensitivity, pneumonitis, severe colitis, infection risk, weight or nutritional effects, and embryo-fetal toxicity requiring reproductive planning.
Monitoring: Because alpelisib can affect how the body processes sugar, patients need baseline testing of their HbA1c and fasting glucose levels before starting, followed by strict regular monitoring ^[10]. Follow the current prescribing information and your prescriber’s specific monitoring schedule, and know which symptoms trigger an urgent call.

Surgical and Orthopedic Interventions

Surgery in PROS is used to solve specific functional problems rather than to cure the condition itself ^[11].

Surgical Debulking: This involves removing excess fat and fibrous tissue to improve appearance or movement ^[5]. It is important to understand that debulking is non-curative; the overgrowth often returns or continues in the surrounding areas after the procedure ^[5]^[12].
Orthopedic Surgery: For limb-length differences, surgeons may perform procedures like epiphysiodesis (slowing the growth of the longer limb) or corrective bone surgery to help with walking and prevent scoliosis ^[13]^[14].
Sclerotherapy: For selected, symptomatic “slow-flow” vascular malformations, an interventional radiologist can perform sclerotherapy. This involves injecting a special liquid into the abnormal vessels to make them shrink or collapse, which can reduce pain and symptoms ^[15]^[16]. Sclerotherapy is not a general preventative measure against blood clots. Perioperative thrombosis prevention and the management of persistent embryonic veins are individualized with a vascular and hematology team.

A Shifting Approach to Care

Doctors may discuss care using a decision aid framework such as PERFORM, which evaluates Patient age, Extent of lesion, Response to treatment, Functional threat, Operative risk, Reconstruction needs, and Multidisciplinary follow-up ^[17].

In some cases, starting alpelisib first may manage a large overgrowth enough to make a later surgery safer or less extensive, though evidence that it reliably avoids surgery is still evolving ^[18]. In other cases, medical therapy might allow a delay in invasive surgery ^[17]. Your team will work with you to decide the highly individualized “sequencing” of these treatments based on your unique growth pattern and functional needs.

Common questions in this guide

What treatments are used for PROS with fibroadipose overgrowth?

Treatment is individualized and may include alpelisib for severe manifestations, surgery to address excess tissue or bone problems, and sclerotherapy for selected symptomatic low-flow vascular malformations. A multidisciplinary vascular anomalies team matches treatment to the person's symptoms, function, age, and treatment risks.

Could I or my child be eligible for alpelisib?

Alpelisib, also called Vijoice, has FDA accelerated approval for adults and children age 2 years or older with severe PIK3CA-related overgrowth spectrum manifestations that require systemic treatment. The treating team decides whether the severity of the overgrowth and the expected benefits and risks fit this treatment.

What monitoring is needed while taking alpelisib?

Before treatment, patients generally need HbA1c and fasting glucose testing, followed by regular blood-sugar monitoring during treatment. Diarrhea, painful mouth sores, high blood sugar, rash, allergic reactions, breathing problems, and severe bowel symptoms should be discussed promptly with the prescribing team.

Does debulking surgery permanently remove the overgrowth?

No. Debulking can remove excess fat and fibrous tissue to improve movement or appearance, but it does not cure the underlying condition. Overgrowth can return or continue in nearby or surrounding areas after surgery.

When is sclerotherapy considered for PROS?

Sclerotherapy may be considered for selected symptomatic slow-flow vascular malformations, using an injection to shrink or collapse abnormal vessels and reduce symptoms such as pain. It is not a general way to prevent blood clots, and clot prevention and persistent embryonic veins require individualized vascular and hematology planning.

How do doctors choose between alpelisib, surgery, and orthopedic treatment?

The team considers age, the extent of overgrowth, response to treatment, threats to function, operative risk, reconstruction needs, and the ability to provide long-term follow-up. Medication may sometimes make later surgery safer or less extensive, but the best sequence is different for each person.

Get notified when new evidence is published on Segmental progressive overgrowth syndrome with fibroadipose hyperplasia.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

References (18)

1
Multidisciplinary Team Care in Plastic Surgery: Vascular Anomalies.
Schmidt JL, Mohan VC, Appel R, et al.
Seminars in plastic surgery 2025; (39(2)):82-88 doi:10.1055/s-0045-1808272.
PMID: 40406638
2
What the Interventional Radiologist Needs to Know about the Genetics of Vascular Anomalies.
Josephs S, Martin L, Josephs T, Hovsepian D
Seminars in interventional radiology 2024; (41(4)):350-362 doi:10.1055/s-0044-1791204.
PMID: 39524236
3
Work-Up and Treatment Strategies for Individuals with PIK3CA-Related Disorders: A Consensus of Experts from the Scientific Committee of the Italian Macrodactyly and PROS Association.
Gazzin A, Leoni C, Viscogliosi G, et al.
Genes 2023; (14(12)) doi:10.3390/genes14122134.
PMID: 38136956
4
FDA Approval Summary: Alpelisib for PIK3CA-Related Overgrowth Spectrum.
Singh S, Bradford D, Li X, et al.
Clinical cancer research : an official journal of the American Association for Cancer Research 2024; (30(1)):23-28 doi:10.1158/1078-0432.CCR-23-1270.
PMID: 37624421
5
PIK3CA-Related Overgrowth Spectrum From Diagnosis to Targeted Therapy: A Case of CLOVES Syndrome Treated With Alpelisib.
Pagliazzi A, Oranges T, Traficante G, et al.
Frontiers in pediatrics 2021; (9()):732836 doi:10.3389/fped.2021.732836.
PMID: 34568242
6
Alpelisib for treatment of patients with PIK3CA-related overgrowth spectrum (PROS).
Canaud G, Lopez Gutierrez JC, Irvine AD, et al.
Genetics in medicine : official journal of the American College of Medical Genetics 2023; (25(12)):100969 doi:10.1016/j.gim.2023.100969.
PMID: 37634128
7
Alpelisib in PIK3CA-Related Overgrowth Spectrum (PROS): A Systematic Review of Real-World Evidence in over 100 Patients.
Pellegrino F, Reynolds G, Cardaropoli S, et al.
Cells 2026; (15(9)) doi:10.3390/cells15090788.
PMID: 42121892
8
Alpelisib in pediatric PIK3CA- and TIE-2-mutant vascular anomalies: a case series on safety, efficacy, and drug exposure.
Etingin A, Remy A, Sonea T, et al.
Pediatric hematology and oncology 2025; (42(4)):228-241 doi:10.1080/08880018.2025.2498660.
PMID: 40346819
9
Alpelisib: A Novel Agent for PIK3CA-Related Overgrowth Spectrum.
Nadjkovic K, Lonabaugh K
The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG 2023; (28(7)):590-594 doi:10.5863/1551-6776-28.7.590.
PMID: 38025143
10
Managing hyperglycemia and rash associated with alpelisib: expert consensus recommendations using the Delphi technique.
Gallagher EJ, Moore H, Lacouture ME, et al.
NPJ breast cancer 2024; (10(1)):12 doi:10.1038/s41523-024-00613-x.
PMID: 38297009
11
A systematic review of the safety and efficacy of currently used treatment modalities in the treatment of patients with PIK3CA-related overgrowth spectrum.
Bernhard SM, Adam L, Atef H, et al.
Journal of vascular surgery. Venous and lymphatic disorders 2022; (10(2)):527-538.e2 doi:10.1016/j.jvsv.2021.07.008.
PMID: 34358672
12
In vitro efficacy of ARQ 092, an allosteric AKT inhibitor, on primary fibroblast cells derived from patients with PIK3CA-related overgrowth spectrum (PROS).
Ranieri C, Di Tommaso S, Loconte DC, et al.
Neurogenetics 2018; (19(2)):77-91 doi:10.1007/s10048-018-0540-1.
PMID: 29549527
13
Congenital difference of the hand and foot: Pediatric macrodactyly.
Shen XF, Gasteratos K, Spyropoulou GA, et al.
Journal of plastic, reconstructive & aesthetic surgery : JPRAS 2022; (75(11)):4054-4062 doi:10.1016/j.bjps.2022.06.059.
PMID: 36175329
14
Evolution over Time of Leg Length Discrepancy in Patients with Syndromic and Isolated Lateralized Overgrowth.
Carli D, De Pellegrin M, Franceschi L, et al.
The Journal of pediatrics 2021; (234()):123-127 doi:10.1016/j.jpeds.2021.01.020.
PMID: 33465347
15
Medical management of vascular anomalies of the head and neck.
Léauté-Labrèze C
Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 2022; (51(10)):837-843 doi:10.1111/jop.13324.
PMID: 35668029
16
Management, Trends, and Recommendations for Intra-abdominal Lymphatic Malformations: A Single-Center Retrospective Review.
Vore E, Cooke-Barber J, Brungardt J, et al.
Journal of pediatric surgery 2025; (60(4)):162223 doi:10.1016/j.jpedsurg.2025.162223.
PMID: 39938181
17
Beyond Lesion Control: A Narrative Review of Targeted Therapy and Surgical Decision-Making in Children With Vascular Anomalies Across Function, Growth, and Perioperative Care.
Altamimi O, Altamimi I, Alhowidi R, et al.
Cureus 2026; (18(6)):e110532 doi:10.7759/cureus.110532.
PMID: 42428199
18
Targeted treatment of severe vascular malformations harboring PIK3CA and TEK mutations with alpelisib is highly effective with limited toxicity.
Sterba M, Pokorna P, Faberova R, et al.
Scientific reports 2023; (13(1)):10499 doi:10.1038/s41598-023-37468-4.
PMID: 37380669

This page is for informational purposes only and does not constitute medical advice. A multidisciplinary vascular anomalies team should tailor alpelisib, surgery, and monitoring to the patient's specific needs.