Yordi-Michaël Bouhatous, Cecilie Bredrup, Agnes Maurer, Liubinka Mirakovska, Alison Foster, Kenjiro Kosaki, Céline Jost, Jean-Baptiste Demoulin, Maxime Luu, Pierre Vabres, Jean-Emmanuel Kurtz, Elise Schaefer, Anne Guimier, Valerie Cormier-Daire, Derek Lim, Sarah Thompson, Lorin Olson, Hae Ryong Kwon, Cristina Aguirre-Rodriguez, Unai Hernandez-Dorronsoro, Itziar Martinez-Soroa, Helena Iznardo, José-Manuel Mascaró, Eulalia Baselga, Silvia Kalantari, Alessandro Mussa, Andrea Gazzin, Diana Carli, Ingrid Svinvik, Hatice Mutlu-Albayrak, Sarah Bluefeather, Yuri Zarate, Toshiki Takenouchi, Thirona Naicker, Antoinette Chateau, Ashmika Gokhul, Anele Dube-Pule, Muzhirah Haniffa, Winnie Ong Peitee, Ann Nordgren, Maud Carpentier, Christine Binquet, Anne-Sophie Briffaut, Laurence Bal, Dinel Pond, Cecilie F Rustad, Marc Bardou, Laurence Faivre
{"title":"“了解和治疗Kosaki/Penttinen综合征”国际合作联盟:关于酪氨酸激酶抑制剂安全性和有效性的随访,自然历史和现实观察研究的建议。","authors":"Yordi-Michaël Bouhatous, Cecilie Bredrup, Agnes Maurer, Liubinka Mirakovska, Alison Foster, Kenjiro Kosaki, Céline Jost, Jean-Baptiste Demoulin, Maxime Luu, Pierre Vabres, Jean-Emmanuel Kurtz, Elise Schaefer, Anne Guimier, Valerie Cormier-Daire, Derek Lim, Sarah Thompson, Lorin Olson, Hae Ryong Kwon, Cristina Aguirre-Rodriguez, Unai Hernandez-Dorronsoro, Itziar Martinez-Soroa, Helena Iznardo, José-Manuel Mascaró, Eulalia Baselga, Silvia Kalantari, Alessandro Mussa, Andrea Gazzin, Diana Carli, Ingrid Svinvik, Hatice Mutlu-Albayrak, Sarah Bluefeather, Yuri Zarate, Toshiki Takenouchi, Thirona Naicker, Antoinette Chateau, Ashmika Gokhul, Anele Dube-Pule, Muzhirah Haniffa, Winnie Ong Peitee, Ann Nordgren, Maud Carpentier, Christine Binquet, Anne-Sophie Briffaut, Laurence Bal, Dinel Pond, Cecilie F Rustad, Marc Bardou, Laurence Faivre","doi":"10.1136/jmg-2024-110600","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>5 years have passed since the formation of the multidisciplinary consortium 'Knowing & Treating Kosaki and Penttinen Syndromes', two ultra-rare degenerative multisystem syndromes caused by heterozygous activating variants in <i>PDGFRB</i>. Neurological, orthopaedic and vascular deterioration can occur. Case reports of patients treated with tyrosine kinase inhibitors (TKIs) suggest that these drugs may be a therapeutic option in the future. The bi-annual remote meetings provide an opportunity to share knowledge on these syndromes.</p><p><strong>Material and methods: </strong>The consortium has validated the communication process, standardised follow-up guidelines, established a database to improve the natural history of these syndromes and evaluated the real-world safety and efficacy profile of TKIs by comparing treated and untreated patients. The regulatory framework is in place.</p><p><strong>Results: </strong>As of November 2024, 18 teams in 13 countries have joined the consortium. More than 25 patients have been identified worldwide, either published or unpublished; 7 of them were treated with a TKI. The guidelines include retrospective and prospective sections for each organ affected by the disease and are based on literature and expert opinion. They also include recommendations to standardise the assessment of the efficacy and safety of treatments prescribed under compassionate use.</p><p><strong>Conclusion: </strong>The consortium welcomes new teams on an ongoing basis. Recommendations are especially useful in such ultra-rare degenerative diseases. The real-life observational study seems to be an appropriate model to improve knowledge, including the assessment of treatment efficacy when the prevalence of the disease does not allow the setting up of clinical trials.</p>","PeriodicalId":16237,"journal":{"name":"Journal of Medical Genetics","volume":" ","pages":"656-663"},"PeriodicalIF":3.7000,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"'Knowing and Treating Kosaki/Penttinen syndrome' international collaborative consortium: recommendations for follow-up, natural history and a real-life observational study about safety and efficacy profile of tyrosine kinase inhibitors.\",\"authors\":\"Yordi-Michaël Bouhatous, Cecilie Bredrup, Agnes Maurer, Liubinka Mirakovska, Alison Foster, Kenjiro Kosaki, Céline Jost, Jean-Baptiste Demoulin, Maxime Luu, Pierre Vabres, Jean-Emmanuel Kurtz, Elise Schaefer, Anne Guimier, Valerie Cormier-Daire, Derek Lim, Sarah Thompson, Lorin Olson, Hae Ryong Kwon, Cristina Aguirre-Rodriguez, Unai Hernandez-Dorronsoro, Itziar Martinez-Soroa, Helena Iznardo, José-Manuel Mascaró, Eulalia Baselga, Silvia Kalantari, Alessandro Mussa, Andrea Gazzin, Diana Carli, Ingrid Svinvik, Hatice Mutlu-Albayrak, Sarah Bluefeather, Yuri Zarate, Toshiki Takenouchi, Thirona Naicker, Antoinette Chateau, Ashmika Gokhul, Anele Dube-Pule, Muzhirah Haniffa, Winnie Ong Peitee, Ann Nordgren, Maud Carpentier, Christine Binquet, Anne-Sophie Briffaut, Laurence Bal, Dinel Pond, Cecilie F Rustad, Marc Bardou, Laurence Faivre\",\"doi\":\"10.1136/jmg-2024-110600\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>5 years have passed since the formation of the multidisciplinary consortium 'Knowing & Treating Kosaki and Penttinen Syndromes', two ultra-rare degenerative multisystem syndromes caused by heterozygous activating variants in <i>PDGFRB</i>. Neurological, orthopaedic and vascular deterioration can occur. Case reports of patients treated with tyrosine kinase inhibitors (TKIs) suggest that these drugs may be a therapeutic option in the future. The bi-annual remote meetings provide an opportunity to share knowledge on these syndromes.</p><p><strong>Material and methods: </strong>The consortium has validated the communication process, standardised follow-up guidelines, established a database to improve the natural history of these syndromes and evaluated the real-world safety and efficacy profile of TKIs by comparing treated and untreated patients. The regulatory framework is in place.</p><p><strong>Results: </strong>As of November 2024, 18 teams in 13 countries have joined the consortium. More than 25 patients have been identified worldwide, either published or unpublished; 7 of them were treated with a TKI. The guidelines include retrospective and prospective sections for each organ affected by the disease and are based on literature and expert opinion. They also include recommendations to standardise the assessment of the efficacy and safety of treatments prescribed under compassionate use.</p><p><strong>Conclusion: </strong>The consortium welcomes new teams on an ongoing basis. Recommendations are especially useful in such ultra-rare degenerative diseases. The real-life observational study seems to be an appropriate model to improve knowledge, including the assessment of treatment efficacy when the prevalence of the disease does not allow the setting up of clinical trials.</p>\",\"PeriodicalId\":16237,\"journal\":{\"name\":\"Journal of Medical Genetics\",\"volume\":\" \",\"pages\":\"656-663\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Medical Genetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/jmg-2024-110600\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medical Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/jmg-2024-110600","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
'Knowing and Treating Kosaki/Penttinen syndrome' international collaborative consortium: recommendations for follow-up, natural history and a real-life observational study about safety and efficacy profile of tyrosine kinase inhibitors.
Background: 5 years have passed since the formation of the multidisciplinary consortium 'Knowing & Treating Kosaki and Penttinen Syndromes', two ultra-rare degenerative multisystem syndromes caused by heterozygous activating variants in PDGFRB. Neurological, orthopaedic and vascular deterioration can occur. Case reports of patients treated with tyrosine kinase inhibitors (TKIs) suggest that these drugs may be a therapeutic option in the future. The bi-annual remote meetings provide an opportunity to share knowledge on these syndromes.
Material and methods: The consortium has validated the communication process, standardised follow-up guidelines, established a database to improve the natural history of these syndromes and evaluated the real-world safety and efficacy profile of TKIs by comparing treated and untreated patients. The regulatory framework is in place.
Results: As of November 2024, 18 teams in 13 countries have joined the consortium. More than 25 patients have been identified worldwide, either published or unpublished; 7 of them were treated with a TKI. The guidelines include retrospective and prospective sections for each organ affected by the disease and are based on literature and expert opinion. They also include recommendations to standardise the assessment of the efficacy and safety of treatments prescribed under compassionate use.
Conclusion: The consortium welcomes new teams on an ongoing basis. Recommendations are especially useful in such ultra-rare degenerative diseases. The real-life observational study seems to be an appropriate model to improve knowledge, including the assessment of treatment efficacy when the prevalence of the disease does not allow the setting up of clinical trials.
期刊介绍:
Journal of Medical Genetics is a leading international peer-reviewed journal covering original research in human genetics, including reviews of and opinion on the latest developments. Articles cover the molecular basis of human disease including germline cancer genetics, clinical manifestations of genetic disorders, applications of molecular genetics to medical practice and the systematic evaluation of such applications worldwide.