Abstract
Objective: To analyze the clinical features, bone marrow features, and gene mutations of children with familial platelet disorder with predisposition to myeloid leukemia (FPD/AML) caused by a RUNX1 germline mutation as well as their family members. Methods: The clinical data and gene mutations of a child with FPD/AML hospitalized in the Pediatric Blood Disease Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and some family members were extracted and analyzed. The literature was searched using "RUNX1 germline mutation" and "FPD/AML" as keywords in the Chinese databases; also PubMed was reviewed until September 2020. Results: A male patient aged 5 with dermatorrhagia was admitted due to thrombocytopenia for more than 3 years. The laboratory tests revealed a peripheral blood routine (WBC 6.38×10(9)/L, HGB 113 g/L, PLT 54×10(9)/L, NEUT 4.03×10(9)/L, and MPV 9.1 fl) . Bone marrow smear revealed dysplasia of megakaryocytes. The immunohistochemistry for CD42b and CD41 highlighted small mononuclear megakaryocytes. Second generation sequencing revealed RUNX1 (exon3:c.520delC: p.R174Efs*10, NM_001001890) frameshift mutations, and its germline mutation was verified via genetic detection of oral epithelial cells. Five members of the family had blood diseases and successively died. The child's mother and maternal grandfather were sequenced for the second generation, and RUNX1 frameshift mutation was detected in the same locus as the child. However, the clinical features among them were different. A total of 37 English literatures were retrieved, and more than 70 FPD/AML families were reported. No relevant Chinese literature was retrieved. Conclusion: Runx1 germline mutations cause FPD/AML with a high risk of progression to myeloid malignancy. Family members carrying the same mutations may exhibit different clinical features and severity.