[DDX41-mutated myeloid neoplasms].

Germline variants of DDX41 are among the most common mutations conferring hereditary predisposition to adult MDS/AML, occurring particularly frequently in MDS with increased blasts and in AML secondary to MDS. Their prevalence across disease subtypes is 3% to 9%, with approximately 60% being germline nonsense or frameshift variants that typically acquire a somatic missense second hit. The variant frequency is 2 to 3 times higher in men, and adverse co-mutations such as those in FLT3 or NRAS are uncommon. Penetrance is nearly 0% by age 40 and approximately 50% by age 90, with comparable estimates in Japanese, UK, and French population datasets. DDX41 variants account for roughly 80% of currently recognized hereditary myeloid predisposition syndromes, and DDX41-mutated MDS is challenging to stratify using IPSS-R or IPSS-M. Hypomethylating agents are effective, and the addition of venetoclax provides substantial therapeutic benefit. Notably, cases of post-transplant leukemia arising from related donors harboring DDX41 variants have been reported, highlighting the clinical importance of presymptomatic mutation screening.