Pediatric Germline Predispositions to Myelodisplastic Syndrome, Expert Guidance for the Initial Evaluation and Management of SAMD9 and SAMD9L Variants, and the Importance of Database Development for these Rare Syndromes

Abstract

Bone marrow failure and hematologic malignancy is rare within the pediatric population. Germline mutations within this population were initially thought to be rare, but we are finding that these malignancies are more likely to have germline predispositions than initially thought. SAMD9/SAMD9L activating (gain or change of function) germline heterozygous mutations are a severe rare blood disorder with malignant potential in need of greater understanding and acute guidelines for diagnosis and therapy. In November 2019, the St. Jude Children’s Research Hospital sponsored the first international symposium on SAMD9/SAMD9L mutations. Forty internationally recognized experts met with the goal to develop a consensus on the diagnosis, monitoring, and management of individuals diagnosed with SAMD9/SAMD9L associated syndromes and carriers within affected families. The group mission was to improve accuracy of diagnosis and the timely detection of complications. A manuscript was then created, using the modified Delphi approach, to reflect the group’s recommendations for the initial evaluation and management of patients suspected to have SAMD9/SAMD9L variants. This manuscript is the first step to improving care for patients with SAMD9/SAMD9L variants. Future research involves a patient registry/natural history prospective study to establish the data required to support the treatment recommendations which are controversial. Database development is an essential part of ensuring these registries are effective at collecting the necessary data. Rare disease registries are essential to comprehensively increase knowledge about disease characteristics, the natural course of these diseases, and assess the long-term outcomes of the patients affected by them.