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The Knowing and Treating Kosaki / Penttinen syndromes study 

The Knowing and Treating Kosaki / Penttinen syndromes study was initiated by Professor Laurence FAIVRE, Head of the Genetics Department at the Dijon Bourgogne University Hospital.

The aim of our study is twofold : to describe the largest international cohort of KOGS/PS patients and to investigate the efficacy and safety of Tyrosine Kinase Inhibitors (TKIs) in these indications.

The Knowing and Treating Kosaki / Penttinen syndromes study 

Knowing and Treating Kosaki/Penttinen is a real-life observational study, which means that it does not change the way the patient is treated by the healthcare team. We are simply observing how the patient's health status evolves during the course of their usual medical follow-up. The referring doctor remains responsible for the suggested medical follow-up.

Depending on the patient's age and state of health, as well as current scientific and medical knowledge, various examinations will be repeated at varying intervals. In particular, the appearance and development of arterial aneurysms will be monitored. The initiation of TKI treatment will remain at the discretion of the referring physician, with the patient's consent and if permitted by national legislation.

During the follow-up, the referring physician fills in the Cleanweb© database from the patient's medical record. The health data will be pseudonymised using a patient identification number, which guarantees the confidentiality and security of the data.

Firstly, it will enable us to improve our knowledge of these diseases by collecting information on symptoms, age of onset, severity, evolution, diagnostic methods used, changes in drug and non-drug management, etc.

In a second phase, we would also like to compare the outcomes of treated and untreated patients to determine on a larger scale and with greater certainty whether TKIs are effective in treating these two diseases.

We want to include as many patients as possible in the study to get a comprehensive picture of these diseases. In addition, to gain as much perspective as possible on the evolution of these diseases and on the safety and efficacy of TKIs, we are planning a minimum study duration of 25 years.


The University Hospital of Dijon Bourgogne is the coordinating centre of the study.

In order to ensure maximum security for the transfer of data to the coordinating centre, each participating centre will have to sign a contract with the coordinating centre setting out the terms and conditions for the transfer of patient data in a document known as a data transfer agreement.

Your follow-up data will not be accessible to other referring physicians, but will be available to the Dijon Bourgogne University Hospital, in the person of Professor Laurence FAIVRE, the principal investigator of the study, and some of her colleagues, to ensure regular documentation of the database and to analyse the data. Any doctor participating in the database can propose to carry out a specific study using the data. In this case, the request is submitted to the consortium and the anonymised data are sent to the doctor who will carry out the work.

Scientific publications 

Prior to the creation of the research project and its consortium, many physicians published their patients' cases in the  scientific literature. 

Several teams have renewed their publications to update knowledge on the evolution of their patients, particularly after the introduction of a TKI.

Attached is a list of the scientific publications on which the preliminary work of the consortium, that set up the Treat Kosaki/Penttinen study, is based.

Untreated patients :

Open access articles :


Johnston JJ, et al. A Point Mutation in PDGFRB Causes Autosomal-Dominant Penttinen Syndrome.   Am J Hum Genet. 2015 Sep 3;97(3):465-74. PMID: 26279204


Zhang Z, et al. Premature Aging Syndrome, Penttinen Type: Report of a Chinese Case with a PDGFRB Mutation. Acta Derm Venereol. 2018 Oct 10;98(9):912-913. PMID: 29944170


Bredrup C, et al. A tyrosine kinase-activating variant Asn666Ser in PDGFRB causes a progeria-like condition in the severe end of Penttinen syndrome. Eur J Hum Genet. 2019 Apr;27(4):574-581. PMID: 30573803


Foster A, et al. Kosaki overgrowth syndrome: A novel pathogenic variant in PDGFRB and expansion of the phenotype including cerebrovascular complications. Clin Genet. 2020 Jul;98(1):19-31. PMID: 32291752


Walker H, et al. Carpal tunnel syndrome in paediatric patients: A novel association with Kosaki overgrowth syndrome. JPRAS Open. 2020 Jul 27;25:83-87. PMID: 32904243


Hernández Dorronsoro U, et al. Kosaki overgrowth syndrome due to a novel de novo PDGFRB variant. Clin Genet. 2022 Jan;101(1):144--145. PMID: 34708400


Mutlu Albayrak H, Calder AD. Kosaki Overgrowth Syndrome: Report of a Family with a Novel PDGFRB Variant. Mol Syndromol. 2022 Feb;13(1):38-44. PMID: 35221873


Articles with restricted access :


Penttinen M, et al. New progeroid disorder. Am J Med Genet. 1997 Mar 17;69(2):182-7. PMID: 9056558


Zufferey F, et al. Acro-osteolysis, keloid like-lesions, distinctive facial features, and overgrowth: two newly recognized patients with premature aging syndrome, Penttinen type. Am J Med Genet A. 2013 Jul;161A(7):1786-91. PMID: 23720404


Abarca H, et al. Ocular pterygium--digital keloid dysplasia. Am J Med Genet A. 2014 Nov;164A(11):2901-7. PMID: 25124224


Takenouchi T, et al. Novel overgrowth syndrome phenotype due to recurrent de novo PDGFRB mutation. J Pediatr. 2015 Feb;166(2):483-6. PMID: 25454926.


Aminkeng F. PDGFRB mutation causes autosomal-dominant Penttinen syndrome.  Clin Genet. 2015 Dec;88(6):531. PMID: 26507258


Minatogawa M, et al. Expansion of the phenotype of Kosaki overgrowth syndrome. Am J Med Genet A. 2017 Sep;173(9):2422-2427. PMID: 28639748


Gawliński P, et al. Phenotype expansion and development in Kosaki overgrowth syndrome. Clin Genet. 2018 Apr;93(4):919-924. PMID: 29226947


Zarate YA, et al. Constitutive activation of the PI3K-AKT pathway and cardiovascular abnormalities in an individual with Kosaki overgrowth syndrome. Am J Med Genet A. 2019 Jun;179(6):1047-1052. PMID: 30941910


Guimier A, et al. A novel de novo PDGFRB variant in a child with severe cerebral malformations, intracerebral calcifications, and infantile myofibromatosis. Am J Med Genet A. 2019 Jul;179(7):1304-1309. PMID: 31004414


Takenouchi T, et al. Kosaki overgrowth syndrome: A newly identified entity caused by pathogenic variants in platelet-derived growth factor receptor-beta. Am J Med Genet C Semin Med Genet. 2019 Dec;181(4):650-657. PMID: 31710779


Takenouchi T, et al. Progressive cerebral and coronary aneurysms in the original two patients with Kosaki overgrowth syndrome. Am J Med Genet A. 2021 Mar;185(3):999-1003. PMID: 33382209


Chenbhanich J, et al. Segmental overgrowth and aneurysms due to mosaic PDGFRB p.(Tyr562Cys). Am J Med Genet A. 2021 May;185(5):1430-1436. PMID: 33683022


Aggarwal B, et al. First case report of Penttinen syndrome from India. Am J Med Genet A. 2022 Feb;188(2):683-687. PMID: 34799960

Treated patients : 

Open access articles :


Pond D, et al. A patient with germ-line gain-of-function PDGFRB p.N666H mutation and marked clinical response to imatinib. Genet Med. 2018 Jan;20(1):142-150. PMID: 28726812


Articles with restricted access :


Wenger TL, et al. Activating variants in PDGFRB result in a spectrum of disorders responsive to imatinib monotherapy. Am J Med Genet A. 2020 Jul;182(7):1576-1591. PMID: 32500973


Rustad CF, et al. Positive response to imatinib in PDGFRB-related Kosaki overgrowth syndrome. Am J Med Genet A. 2021 Aug;185(8):2597-2601. PMID: 33979467


Iznardo H, et al. Clinical and molecular response to dasatinib in an adult patient with Penttinen syndrome. Am J Med Genet A. 2022 Apr;188(4):1233-1238. PMID: 34894066

Functionnal in vitro cellular studies :

Open access articles :


He C, et al. STAT1 modulates tissue wasting or overgrowth downstream from PDGFRβ. Genes Dev. 2017 Aug 15;31(16):1666-1678. PMID: 28924035


Bredrup C, et al. Temperature-dependent autoactivation associated with clinical variability of PDGFRB Asn666 substitutions. Hum Mol Genet. 2021 Mar 25;30(1):72-77. PMID: 33450762


Nédélec A, et al. Penttinen syndrome-associated PDGFRB Val665Ala variant causes aberrant constitutive STAT1 signalling. J Cell Mol Med. 2022 Jul;26(14):3902-3912. PMID: 35689379


Articles with restricted access :


Moura DAP, et al. The Master of Puppets: Pleiotropy of PDGFRB and its Relationship to Multiple Diseases. J Mol Neurosci. 2020 Dec;70(12):2102-2106. PMID: 32613555


Guérit E, et al. PDGF receptor mutations in human diseases. Cell Mol Life Sci. 2021 Apr;78(8):3867-3881. PMID: 33449152 Review.

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