Knowing and Treating Kosaki/Penttinen Syndromes

Study Overview
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Brief Summary
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Kosaki overgrowth syndrome (KOGS) and Penttinen syndrome (PS) are extremely rare multisystem disorders caused by heterozygous activating variants of the PDGFRB gene. KOGS results in characteristic craniofacial, orthopedic, skin and neurological disorders. PS is a progeroid disease responsible for a prematurely aged appearance. Patients suffer significant morbidity and mortality due to various complications. Tyrosine Kinase Inhibitors (TKIs) targeting PGDFRB appear to be a potential treatment option, as evidenced by a few case reports showing clinical improvement in some patients, with modest and self-resolving side effects. The natural history of these two syndromes remains poorly understood as only case-reports have been published. Therefore, an international consortium was created in December 2019 by Pr FAIVRE (CHU Dijon Bourgogne & ERN ITHACA) to follow treated and untreated patients in a real-life, multicentre, observational study, in order to expand our knowledge of these ultra-rare diseases. In the longer term, we believe that TKIs could bring clinical benefit to KOGS/PS patients.

Official Title
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 Knowing & Treating Kosaki/Penttinen Syndromes  International Collaborative Consortium. A Real-life Observational Study on the Natural History of KOGS and PS and on the Efficacy and Safety Profile of TKIs in These Patients.

Conditions
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Kosaki Overgrowth Syndrome, Penttinen Syndrome

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of Kosaki or Penttinen syndrome Molecular diagnosis of an activating variant in PDGFRB gene Patient who has been informed and provide a written informed consent Exclusion Criteria: Absence of clinical diagnosis of Kosaki or Penttinen syndrome Absence of molecular diagnosis of an activating variant in the PDGFRB gene. Patient who has not been informed and/or did not provide a written informed consent.

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Untreated<br>Not treated with TKI | |
| Treated<br>Treated with TKI | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom's burden | Symptoms: type, severity, date of appearance, evolution | At various time points according to the type of symptom: from weekly to every 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of TKI | Proportion of patients with improvement in quality of life under TKI treatment, expressed as percentages | Through the study completion, an average of 10 years. | 
| Safety of TKI | Proportion of patients with side effects under TKI treatment, expressed as percentages | Through the study completion, an average of 10 years. | 
| Percentage of patients whose follow-up complies with recommendations |  | Through the study completion, an average of 10 years. | 
| Percentage of patients whose TKI has been chosen according to cellular studies |  | Through the study completion, an average of 10 years. |