ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 73 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Nonrandomized Open Label Pilot Study of Sirolimus Therapy for Segmental Overgrowth Caused by Somatic PI3K Activation
Non-randomised Open Label Pilot Study of Sirolimus Therapy for Segmental Overgrowth Due to PIK3CA- Related Overgrowth
Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- Pooled it
- Safety findings from the phase 1/2 MOSAIC study of miransertib for patients with PIK3CA-related overgrowth spectrum or Proteus syndrome.Orphanet journal of rare diseases · 2025Trial
- Safety and efficacy of low-dose PI3K inhibitor taselisib in adult patients with CLOVES and Klippel-Trenaunay syndrome (KTS): the TOTEM trial, a phase 1/2 multicenter, open-label, single-arm study.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Trial
- Clinical experience with the AKT1 inhibitor miransertib in two children with PIK3CA-related overgrowth syndrome.Orphanet journal of rare diseases · 2021Trial
- Case Report: First report of PIK3CA-related overgrowth spectrum revealed by refractory chylorrhea after breast-conserving surgery: failed thoracic-duct ligation.Frontiers in surgery · 2026Article
- PI3K/AKT/mTOR axis in vascular malformations: from molecular insights to targeted clinical trials.Orphanet journal of rare diseases · 2025Review
- Pharmacovigilance analysis of vision disorders relating to brimonidine treatment and mechanism study using network toxicology and molecular docking.Scientific reports · 2025Article
- Effective Sirolimus Use in Prenatal and Postnatal Management of Symptomatic Extensive Congenital Capillary-Lymphatic-Venous Malformations (CLVMs): A Report of Two Cases.Paediatric drugs · 2025Article
- Quantification of Lateralized Overgrowth and Genotype-Driven Tissue Composition.Clinical genetics · 2025Article
- mTOR pathway diseases: challenges and opportunities from bench to bedside and the mTOR node.Orphanet journal of rare diseases · 2025Review
- An Extremely Preterm Infant WithCase reports in genetics · 2025Article
- Low lymphozyte pool, colon perforation and hydrocephalus as clinical features in an infant with a postzygoticFrontiers in pediatrics · 2025Article
- Article
- An immortalized adipose-derived stem cells line from theBiochemistry and biophysics reports · 2024Article
- Sirolimus reduces T cell cycling, immune checkpoint marker expression, and HIV-1 DNA in people with HIV.Cell reports. Medicine · 2024Article
- A cystic and bullous lung disease associated with a PIK3CA-related overgrowth syndrome.ERJ open research · 2024Article
- Real-World Data on the Use of Sirolimus in Asian Children with Vascular Malformations.Paediatric drugs · 2024Article
- Treatment of hypoglycemia due to a rare pathogenic variant inClinical case reports · 2024Article
- PIK3CA regulates development of diabetes retinopathy through the PI3K/Akt/mTOR pathway.PloS one · 2024Article
- Infection risk in patients with autoimmune cytopenias and immune dysregulation treated with mycophenolate mofetil and sirolimus.Frontiers in immunology · 2024Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
32 authors at 13 institutions in 3 countries.
Funding
Abstract
purposePIK3CA-related overgrowth spectrum (PROS) encompasses a range of debilitating conditions defined by asymmetric overgrowth caused by mosaic activating PIK3CA variants. PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K), a critical transducer of growth factor signaling. As mTOR mediates the growth-promoting actions of PI3K, we hypothesized that the mTOR inhibitor sirolimus would slow pathological overgrowth.
methodsThirty-nine participants with PROS and progressive overgrowth were enrolled into open-label studies across three centers, and results were pooled. For the primary outcome, tissue volumes at affected and unaffected sites were measured by dual energy X-ray absorptiometry during 26 weeks of untreated run-in and 26 weeks of sirolimus therapy.
resultsThirty participants completed the study. Sirolimus led to a change in mean percentage total tissue volume of -7.2% (SD 16.0, p = 0.04) at affected sites, but not at unaffected sites (+1.7%, SD 11.5, p = 0.48) (n = 23 evaluable). Twenty-eight of 39 (72%) participants had ≥1 adverse event related to sirolimus of which 37% were grade 3 or 4 in severity and 7/39 (18%) participants were withdrawn consequently.
conclusionThis study suggests that low-dose sirolimus can modestly reduce overgrowth, but cautions that the side-effect profile is significant, mandating individualized risk-benefit evaluations for sirolimus treatment in PROS.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.