{
  "abstract": "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 More than 25 patients have been identified worldwide, either published or unpublished; 7 of them were treated with a TKI.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.",
  "authors": [
    {
      "affiliations": [
        "Université Bourgogne Europe, CHU Dijon Bourgogne, Inserm, CTM UMR1231, équipe GAD, FHU TRANSLAD, Centre de génétique, Centre de référence Anomalies du Développement et Syndromes Malformatifs, 21000 Dijon, France"
      ],
      "name": "Yordi-Michaël Bouhatous"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Haukeland University Hospital, Bergen, Norway",
        "Department of Clinical Medicine, University of Bergen, Bergen, Norway"
      ],
      "name": "Cecilie Bredrup"
    },
    {
      "affiliations": [
        "Université Bourgogne Europe, CHU Dijon Bourgogne, Inserm, CTM UMR1231, équipe GAD, FHU TRANSLAD, Centre de génétique, Centre de référence Anomalies du Développement et Syndromes Malformatifs, 21000 Dijon, France"
      ],
      "name": "Agnes Maurer"
    },
    {
      "affiliations": [
        "Université Bourgogne Europe, CHU Dijon Bourgogne, Inserm, CTM UMR1231, équipe GAD, FHU TRANSLAD, Centre de génétique, Centre de référence Anomalies du Développement et Syndromes Malformatifs, 21000 Dijon, France"
      ],
      "name": "Liubinka Mirakovska"
    },
    {
      "affiliations": [
        "West Midlands Regional Genetics Service, Birmingham Women's and Children’s NHS Foundation Trust, Birmingham, UK"
      ],
      "name": "Alison Foster"
    },
    {
      "affiliations": [
        "Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan"
      ],
      "name": "Kenjiro Kosaki"
    },
    {
      "affiliations": [
        "Université Bourgogne Europe, CHU Dijon Bourgogne, Inserm, CTM UMR1231, équipe GAD, FHU TRANSLAD, Centre de génétique, Centre de référence Anomalies du Développement et Syndromes Malformatifs, 21000 Dijon, France"
      ],
      "name": "Céline Jost"
    },
    {
      "affiliations": [
        "De Duve Institute, Université Catholique de Louvain, Brussels, Belgium"
      ],
      "name": "Jean-Baptiste Demoulin"
    },
    {
      "affiliations": [
        "Université Bourgogne Europe, CHU Dijon Bourgogne, Inserm CTM UMR1231, équipe GAD, FHU TRANSLAD, Inserm 1432 Centre d’investigation clinique module Plurithématique (CIC-P), 21 000 Dijon, France"
      ],
      "name": "Maxime Luu"
    },
    {
      "affiliations": [
        "Université Bourgogne Europe, CHU Dijon Bourgogne, Inserm, CTM UMR1231, équipe GAD, FHU TRANSLAD, Centre de référence des maladies rares de la peau et des muqueuses d'origine génétique, 21000 Dijon, France"
      ],
      "name": "Pierre Vabres"
    },
    {
      "affiliations": [
        "Departement of medico-surgical oncology and hematology, Strasbourg Cancer Institute ICANS, INSERMU4113, Strasbourg, France"
      ],
      "name": "Jean-Emmanuel Kurtz"
    },
    {
      "affiliations": [
        "Hôpitaux Universitaires de Strasbourg, Service de Génétique Médicale, Strasbourg, France"
      ],
      "name": "Elise Schaefer"
    },
    {
      "affiliations": [
        "Service de Médecine Genomique des Maladies Rares, CRMR Anomalies Du Développement, Hôpital Necker-Enfants Malades, Assistance Publique des Hôpitaux de Paris, Paris, Île-de-France, France"
      ],
      "name": "Anne Guimier"
    },
    {
      "affiliations": [
        "Department of Medical Genetics, Paris Descartes University, INSERM UMR 1163, Imagine Institute, Necker Enfants Malades Hospital, Paris, France"
      ],
      "name": "Valerie Cormier-Daire"
    },
    {
      "affiliations": [
        "West Midlands Regional Genetics Service, Birmingham Women's and Children’s NHS Foundation Trust, Birmingham, UK"
      ],
      "name": "Derek Lim"
    },
    {
      "affiliations": [
        "West Midlands Regional Genetics Service, Birmingham Women's and Children’s NHS Foundation Trust, Birmingham, UK"
      ],
      "name": "Sarah Thompson"
    },
    {
      "affiliations": [
        "Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA"
      ],
      "name": "Lorin Olson"
    },
    {
      "affiliations": [
        "Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA"
      ],
      "name": "Hae Ryong Kwon"
    },
    {
      "affiliations": [
        "Internal Medicine Department, Donostia University Hospital Aranzazu Building, San Sebastián, PV, Spain"
      ],
      "name": "Cristina Aguirre-Rodriguez"
    },
    {
      "affiliations": [
        "Pediatrics Department, Donostia University Hospital, Donostia-San Sebastián, Spain"
      ],
      "name": "Unai Hernandez-Dorronsoro"
    },
    {
      "affiliations": [
        "Ophthalmology Department, Donostia University Hospital, Donostia-San Sebastián, Spain"
      ],
      "name": "Itziar Martinez-Soroa"
    },
    {
      "affiliations": [
        "Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain"
      ],
      "name": "Helena Iznardo"
    },
    {
      "affiliations": [
        "Department of Dermatology, Hospital Clínic de Barcelona, Barcelona, Spain"
      ],
      "name": "José-Manuel Mascaró"
    },
    {
      "affiliations": [
        "Department of Dermatology, Hospital Sant Joan de Déu, Barcelona, Spain"
      ],
      "name": "Eulalia Baselga"
    },
    {
      "affiliations": [
        "Department of Molecular Medicine, University of Pavia, Pavia, Italy"
      ],
      "name": "Silvia Kalantari"
    },
    {
      "affiliations": [
        "Department of Public Health and Pediatric Sciences, University of Torino, Torino, Italy"
      ],
      "name": "Alessandro Mussa"
    },
    {
      "affiliations": [
        "Department of Public Health and Pediatric Sciences, University of Torino, Torino, Italy"
      ],
      "name": "Andrea Gazzin"
    },
    {
      "affiliations": [
        "Department of Public Health and Pediatric Sciences, University of Torino, Torino, Italy"
      ],
      "name": "Diana Carli"
    },
    {
      "affiliations": [
        "Department of pediatrics, Oslo University Hospital, Rikshospitalet, Oslo, Norway"
      ],
      "name": "Ingrid Svinvik"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Division of Pediatric Genetics, Ankara University School of medicine, Ankara, Ankara, Turkey"
      ],
      "name": "Hatice Mutlu-Albayrak"
    },
    {
      "affiliations": [
        "Paediatrics, Hervey Bay and Maryborough Hospital, Maryborough, Queensland, Australia"
      ],
      "name": "Sarah Bluefeather"
    },
    {
      "affiliations": [
        "Section of Genetics and Metabolism, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA",
        "Division of Genetics and Metabolism, University of Kentucky, Lexington, Kentucky, USA"
      ],
      "name": "Yuri Zarate"
    },
    {
      "affiliations": [
        "Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan"
      ],
      "name": "Toshiki Takenouchi"
    },
    {
      "affiliations": [
        "Inkosi Albert Luthuli Central Hospital, Durban, South Africa"
      ],
      "name": "Thirona Naicker"
    },
    {
      "affiliations": [
        "Inkosi Albert Luthuli Central Hospital, Durban, South Africa"
      ],
      "name": "Antoinette Chateau"
    },
    {
      "affiliations": [
        "Inkosi Albert Luthuli Central Hospital, Durban, South Africa"
      ],
      "name": "Ashmika Gokhul"
    },
    {
      "affiliations": [
        "Inkosi Albert Luthuli Central Hospital, Durban, South Africa"
      ],
      "name": "Anele Dube-Pule"
    },
    {
      "affiliations": [
        "Department of genetics, Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia"
      ],
      "name": "Muzhirah Haniffa"
    },
    {
      "affiliations": [
        "Department of genetics, Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia"
      ],
      "name": "Winnie Ong Peitee"
    },
    {
      "affiliations": [
        "Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden"
      ],
      "name": "Ann Nordgren"
    },
    {
      "affiliations": [
        "CHU Dijon Bourgogne, Direction de la Recherche Clinique et de l’Innovation, Dijon, Bourgogne-Franche-Comté, France"
      ],
      "name": "Maud Carpentier"
    },
    {
      "affiliations": [
        "Université Bourgogne Europe, CHU Dijon Bourgogne, Inserm CTM UMR1231, équipe GAD, FHU TRANSLAD, Inserm 1432 Centre d’investigation clinique module Plurithématique (CIC-P), 21 000 Dijon, France"
      ],
      "name": "Christine Binquet"
    },
    {
      "affiliations": [
        "Université Bourgogne Europe, CHU Dijon Bourgogne, Inserm, CTM UMR1231, équipe GAD, FHU TRANSLAD, Inserm 1432 Centre d’investigation clinique module Epidemiologie Clinique (CIC-EC), 21 000 Dijon, France"
      ],
      "name": "Anne-Sophie Briffaut"
    },
    {
      "affiliations": [
        "Centre constitutif syndromes de Marfan et Apparentés region PACA - Centre Aorte Timone, Assistance Publique - Hopitaux de Marseille, Marseille, Provence-Alpes-Côte d’Azur, France"
      ],
      "name": "Laurence Bal"
    },
    {
      "affiliations": [
        "Department of Medical Genetics and Genomics, Children’s Minnesota, Minneapolis, Minnesota, USA"
      ],
      "name": "Dinel Pond"
    },
    {
      "affiliations": [
        "Department of Medical Genetics, Oslo University Hospital, Oslo, Norway"
      ],
      "name": "Cecilie F Rustad"
    },
    {
      "affiliations": [
        "Université Bourgogne Europe, CHU Dijon Bourgogne, Inserm CTM UMR1231, équipe GAD, FHU TRANSLAD, Inserm 1432 Centre d’investigation clinique module Plurithématique (CIC-P), 21 000 Dijon, France"
      ],
      "name": "Marc Bardou"
    },
    {
      "affiliations": [
        "Université Bourgogne Europe, CHU Dijon Bourgogne, Inserm, CTM UMR1231, équipe GAD, FHU TRANSLAD, Centre de génétique, Centre de référence Anomalies du Développement et Syndromes Malformatifs, 21000 Dijon, France"
      ],
      "name": "Laurence Faivre"
    }
  ],
  "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",
  "uid": "101a8ca2-cc38-55ed-80d4-fd3f8c080e37"
}