Research & Literature

Molecular and Functional Characterization of Three Different Postzygotic Mutations in PIK3CA-Related Overgrowth Spectrum (PROS) Patients: Effects on PI3K/AKT/mTOR Signaling and Sensitivity to PIK3 Inhibitors.

Loconte DC, Grossi V, Bozzao C, et al.

PloS one 2015; (10(4)):e0123092 doi:10.1371/journal.pone.0123092.

Nephroblastomatosis or Wilms tumor in a fourth patient with a somatic PIK3CA mutation.

Gripp KW, Baker L, Kandula V, et al.

American journal of medical genetics. Part A 2016; (170(10)):2559-69 doi:10.1002/ajmg.a.37758.

Utility of clinical high-depth next generation sequencing for somatic variant detection in the PIK3CA-related overgrowth spectrum.

Hucthagowder V, Shenoy A, Corliss M, et al.

Clinical genetics 2017; (91(1)):79-85 doi:10.1111/cge.12819.

Molecular diagnosis of PIK3CA-related overgrowth spectrum (PROS) in 162 patients and recommendations for genetic testing.

Kuentz P, St-Onge J, Duffourd Y, et al.

Genetics in medicine : official journal of the American College of Medical Genetics 2017; (19(9)):989-997 doi:10.1038/gim.2016.220.

Sonographic screening for Wilms tumor in children with CLOVES syndrome.

Peterman CM, Fevurly RD, Alomari AI, et al.

Pediatric blood & cancer 2017; (64(12)) doi:10.1002/pbc.26684.

Characterization of thrombosis in patients with Proteus syndrome.

Keppler-Noreuil KM, Lozier JN, Sapp JC, Biesecker LG

American journal of medical genetics. Part A 2017; (173(9)):2359-2365 doi:10.1002/ajmg.a.38311.

Gait disturbance and lower limb pain in a patient with PIK3CA-related disorder.

Cappuccio G, Alagia M, D'Anna M, et al.

European journal of medical genetics 2017; (60(12)):655-657 doi:10.1016/j.ejmg.2017.08.018.

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.

Characterization of a severe case of PIK3CA-related overgrowth at autopsy by droplet digital polymerase chain reaction and report of PIK3CA sequencing in 22 patients.

Piacitelli AM, Jensen DM, Brandling-Bennett H, et al.

American journal of medical genetics. Part A 2018; (176(11)):2301-2308 doi:10.1002/ajmg.a.40487.

Pharmacodynamic Study of Miransertib in Individuals with Proteus Syndrome.

Keppler-Noreuil KM, Sapp JC, Lindhurst MJ, et al.

American journal of human genetics 2019; (104(3)):484-491 doi:10.1016/j.ajhg.2019.01.015.

Old treatments for new genetic conditions: Sirolimus therapy in a child affected by mosaic overgrowth with fibroadipose hyperplasia.

Leoni C, Onesimo R, Resta N, et al.

Clinical genetics 2019; (96(1)):102-103 doi:10.1111/cge.13550.

Deep vein thrombosis: update on diagnosis and management.

Kruger PC, Eikelboom JW, Douketis JD, Hankey GJ

The Medical journal of Australia 2019; (210(11)):516-524 doi:10.5694/mja2.50201.

Molecular heterogeneity of the cerebriform connective tissue nevus in mosaic overgrowth syndromes.

Keppler-Noreuil KM, Burton-Akright J, Lindhurst MJ, et al.

Cold Spring Harbor molecular case studies 2019; (5(4)) doi:10.1101/mcs.a004036.

Thrombosis risk factors in PIK3CA-related overgrowth spectrum and Proteus syndrome.

Keppler-Noreuil KM, Lozier J, Oden N, et al.

American journal of medical genetics. Part C, Seminars in medical genetics 2019; (181(4)):571-581 doi:10.1002/ajmg.c.31735.

A dyadic genotype-phenotype approach to diagnostic criteria for Proteus syndrome.

Sapp JC, Buser A, Burton-Akright J, et al.

American journal of medical genetics. Part C, Seminars in medical genetics 2019; (181(4)):565-570 doi:10.1002/ajmg.c.31744.

Wound-Healing Problems Associated with Combined Vascular Malformations in Klippel-Trenaunay Syndrome.

Ishikawa K, Yamamoto Y, Funayama E, et al.

Advances in wound care 2019; (8(6)):246-255 doi:10.1089/wound.2018.0835.

PIK3CA vascular overgrowth syndromes: an update.

Hughes M, Hao M, Luu M

Current opinion in pediatrics 2020; (32(4)):539-546 doi:10.1097/MOP.0000000000000923.

Detailed analysis of phenotypes and genotypes in megalencephaly-capillary malformation-polymicrogyria syndrome caused by somatic mosaicism of PIK3CA mutations.

Park HJ, Shin CH, Yoo WJ, et al.

Orphanet journal of rare diseases 2020; (15(1)):205 doi:10.1186/s13023-020-01480-y.

Parkes Weber syndrome associated with two somatic pathogenic variants in RASA1.

Flores Daboub JA, Grimmer JF, Frigerio A, et al.

Cold Spring Harbor molecular case studies 2020; (6(4)) doi:10.1101/mcs.a005256.

Characterization and Childhood Tumor Risk Assessment of Genetic and Epigenetic Syndromes Associated With Lateralized Overgrowth.

Griff JR, Duffy KA, Kalish JM

Frontiers in pediatrics 2020; (8()):613260 doi:10.3389/fped.2020.613260.

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.

Clinical experience with the AKT1 inhibitor miransertib in two children with PIK3CA-related overgrowth syndrome.

Forde K, Resta N, Ranieri C, et al.

Orphanet journal of rare diseases 2021; (16(1)):109 doi:10.1186/s13023-021-01745-0.

Non-hotspot PIK3CA mutations are more frequent in CLOVES than in common or combined lymphatic malformations.

Brouillard P, Schlögel MJ, Homayun Sepehr N, et al.

Orphanet journal of rare diseases 2021; (16(1)):267 doi:10.1186/s13023-021-01898-y.

A review of mechanisms of disease across PIK3CA-related disorders with vascular manifestations.

Canaud G, Hammill AM, Adams D, et al.

Orphanet journal of rare diseases 2021; (16(1)):306 doi:10.1186/s13023-021-01929-8.

A standard of care for individuals with PIK3CA-related disorders: An international expert consensus statement.

Douzgou S, Rawson M, Baselga E, et al.

Clinical genetics 2022; (101(1)):32-47 doi:10.1111/cge.14027.

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.

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.

Venous Thromboembolism for the Practicing Cardiologist.

Pribish AM, Secemsky EA, Schmaier AA

Cardiology clinics 2021; (39(4)):551-566 doi:10.1016/j.ccl.2021.06.008.

Complex vascular anomalies and tissue overgrowth of limbs associated with increased skin temperature and peripheral venous dilatation: parks weber syndrome or PROS?

Su LX, Sun Y, Wang Z, et al.

Hereditas 2022; (159(1)):1 doi:10.1186/s41065-021-00217-6.

Development and validation of a prediction model to estimate risk of acute pulmonary embolism in deep vein thrombosis patients.

Li Y, He Y, Meng Y, et al.

Scientific reports 2022; (12(1)):649 doi:10.1038/s41598-021-04657-y.

Activating PIK3CA postzygotic mutations in segmental overgrowth of muscles with bone involvement in the body extremities.

Tian W, Sun L, Zhang Q, et al.

Molecular genetics and genomics : MGG 2022; (297(2)):387-396 doi:10.1007/s00438-022-01853-x.

Genotypes and phenotypes heterogeneity in PIK3CA-related overgrowth spectrum and overlapping conditions: 150 novel patients and systematic review of 1007 patients with PIK3CA pathogenetic variants.

Mussa A, Leoni C, Iacoviello M, et al.

Journal of medical genetics 2023; (60(2)):163-173 doi:10.1136/jmedgenet-2021-108093.

A Review on Cutaneous and Musculoskeletal Manifestations of CLOVES Syndrome.

Öztürk Durmaz E, Demircioğlu D, Yalınay Dikmen P, et al.

Clinical, cosmetic and investigational dermatology 2022; (15()):621-630 doi:10.2147/CCID.S351637.

Mapping the PIK3CA-related overgrowth spectrum (PROS) patient and caregiver journey using a patient-centered approach.

Rodríguez-Laguna L, Davis K, Finger M, et al.

Orphanet journal of rare diseases 2022; (17(1)):189 doi:10.1186/s13023-022-02338-1.

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.

Qualitative research with patients and caregivers of patients with PIK3CA related overgrowth spectrum: content validity of clinical outcome assessments.

Raymond K, Vallow S, Saucier C, et al.

Journal of patient-reported outcomes 2022; (6(1)):75 doi:10.1186/s41687-022-00481-8.

Brain Abnormalities in PIK3CA-Related Overgrowth Spectrum: Physician, Patient, and Caregiver Experiences.

Dexheimer J, Mirzaa GM

Advances in therapy 2022; (39(9)):3871-3880 doi:10.1007/s12325-022-02246-7.

Alpelisib for the treatment of PIK3CA-related head and neck lymphatic malformations and overgrowth.

Wenger TL, Ganti S, Bull C, et al.

Genetics in medicine : official journal of the American College of Medical Genetics 2022; (24(11)):2318-2328 doi:10.1016/j.gim.2022.07.026.

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.

Clinical Response to PI3K-α Inhibition in a Cohort of Children and Adults With PIK3CA-Related Overgrowth Spectrum Disorders.

Raghavendran P, Albers SE, Phillips JD, et al.

Journal of vascular anomalies 2022; (3(1)) doi:10.1097/jova.0000000000000038.

PIK3CA Mutational Analysis in Patients With Macrodactyly.

Becker J, Gross UC, Weber DM, et al.

Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 2022; (25(6)):624-634 doi:10.1177/10935266221080155.

PIK3CA gain-of-function mutation in adipose tissue induces metabolic reprogramming with Warburg-like effect and severe endocrine disruption.

Ladraa S, Zerbib L, Bayard C, et al.

Science advances 2022; (8(49)):eade7823 doi:10.1126/sciadv.ade7823.

Right Lower Extremity Phlegmasia Cerulea Dolens Due to Iliotibial Vein Thrombosis With Compartment Syndrome and Circulatory Shock: Case Report and Review.

Dah K, Ogbu IR, Ngwudike C, Tripathi M

Cureus 2022; (14(12)):e32364 doi:10.7759/cureus.32364.

Epidemiology of the disorders of the Pik3ca-related overgrowth spectrum (Pros).

Reynolds G, Cardaropoli S, Carli D, et al.

European journal of human genetics : EJHG 2023; (31(11)):1333-1336 doi:10.1038/s41431-023-01414-9.

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.

Clinical and auxological characteristics and quality of life of 50 children and adolescents with segmental overgrowth syndromes at a single center.

Wolf MV, Moresco AA, Fano V, Caino S

Archivos argentinos de pediatria 2023; (121(6)):e202303017 doi:10.5546/aap.2023-03017.eng.

Low risk of embryonic and other cancers in PIK3CA-related overgrowth spectrum: Impact on screening recommendations.

Faivre L, Crépin JC, Réda M, et al.

Clinical genetics 2023; (104(5)):554-563 doi:10.1111/cge.14410.

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.

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.

Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel-Trenaunay syndrome in an Asian population : List the full names and institutional addresses for all authors.

Sasaki Y, Ishikawa K, Hatanaka KC, et al.

Orphanet journal of rare diseases 2023; (18(1)):270 doi:10.1186/s13023-023-02893-1.

Molecular characterization of 13 patients with PIK3CA-related overgrowth spectrum using a targeted deep sequencing approach.

de Kock L, Cuillerier A, Gillespie M, et al.

American journal of medical genetics. Part A 2024; (194(3)):e63466 doi:10.1002/ajmg.a.63466.

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.

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.

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.

Macrodactyly.

Giżewska-Kacprzak K, Śliwiński M, Nicieja K, et al.

Children (Basel, Switzerland) 2024; (11(7)) doi:10.3390/children11070753.

SOLAMEN syndrome with cardiovascular damage.

Zhao X, Yue X, Yuan S, et al.

Hereditas 2024; (161(1)):24 doi:10.1186/s41065-024-00314-2.

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.

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.

Venous thrombosis related to duplicated inferior vena cava: A case report and systematic review.

Chen C, Huang DS, Chang KS, et al.

Medicine 2025; (104(9)):e41748 doi:10.1097/MD.0000000000041748.

Pulmonary embolism after shoulder surgery: Is it a real threat?

Pitsilos C, Papadopoulos P, Givissis P, Chalidis B

World journal of methodology 2025; (15(1)):98343 doi:10.5662/wjm.v15.i1.98343.

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.

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.

Health-Related Quality of Life and Symptom Severity Among Patients With PIK3CA-Related Overgrowth Spectrum: A Mixed-Methods Study to Understand Real-World Experience With Alpelisib Treatment.

Bollu V, LaGasse K, Saucier CD, et al.

Pediatric blood & cancer 2026; (73(8)):e70368 doi:10.1002/1545-5017.70368.

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.

Mosaic Variant in Unilateral Woolly Hair in a Girl With PIK3CA-Related Overgrowth Spectrum.

Tanaka R, Takeguchi R, Akaba Y, et al.

Congenital anomalies 2026; (66(1)):e70066.

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.

Radiological evaluation of the natural history of PIK3CA-related overgrowth spectrum (PROS).

Fraissenon A, Morin G, Boddaert N, et al.

European journal of radiology 2026; (204()):113108 doi:10.1016/j.ejrad.2026.113108.

Clinical and molecular characterization of non-PIK3CA-related vascular malformations with overgrowth in a pediatric cohort.

Reynolds G, Luca M, Coppo P, et al.

World journal of pediatrics : WJP 2026; (22(9)):1024-1039 doi:10.1007/s12519-026-01098-3.

Deep Intramuscular Vascular Malformations in Pediatric Klippel-Trenaunay Syndrome Mimicking Maffucci Syndrome: A Case Report.

Shah SS, Sajid B, Tabassum M, et al.

Clinical case reports 2026; (14(11)):e73825 doi:10.1002/ccr3.73825.