Tyrosine kinase inhibitors in Kosaki/Penttinen syndromes: new reports, follow-up of treated individuals and literature review.

Heterozygous activating variants in platelet-derived growth factor receptor beta (PDGFRβ) are associated with ultra-rare and clinically heterogeneous conditions, including KOGS (Kosaki Overgrowth Syndrome), PS (Penttinen Syndrome) and related conditons. Tyrosine kinase inhibitors (TKIs), which are widely used in hematological and oncological diseases, are now being explored as potential treatments for these conditions. While four published cases have reported encouraging results, there is still insufficient data available to draw definitive conclusions on the benefit-risk ratio. The international consortium Knowing and Treating KOGS/PS was launched to assess the real-life outcomes of such treatments. The consortium presents four new cases and updates four previously published cases of KOGS/PS treated with TKIs from seven countries. A recent publication was also included in the analysis. Individuals received treatment for between three and a half months and eight years (imatinib N = 8/8, dasatinib N = 3/8, sunitinib N = 1/8), with a mean duration of 44.4 months (SD = 29.8). The age at treatment initiation ranged from 6 to 57 years (six patients treated in childhood and two in adulthood). All individuals showed improvement within weeks/months, with minimal side effects. However, efficacy decreased over time in some cases, prompting a switch to a different TKI. These preliminary findings highlight the potential of TKIs for managing KOGS/PS patients. Standardized follow-up protocols and an electronic Case Report Form (eCRF) have been implemented to enhance monitoring and data collection, enabling systematic comparisons between treated and untreated individuals despite the disorders' rarity.