Clinical characterization and genetic analysis of transient abnormal myelopoiesis without the down syndrome phenotype

Transient abnormal myelopoiesis (TAM) is a congenital leukemia specific to neonates with Down syndrome (DS) or trisomy 21. However, rare cases of TAM can also occur with acquired trisomy 21 mutations or mosaic trisomy 21, leading to potential misdiagnosis due to the absence of the DS phenotypes.

We present a case of TAM in a neonate without typical DS phenotypic features. We documented medical records from hospitalizations and a one-year follow-up period. Additionally, through a literature review, we summarized the clinical phenotype and genotypic characteristics observed in similar neonates.

Despite the lack of typical DS phenotype the neonate was diagnosed with TAM upon detection of trisomy 21 and the GATA1 gene mutation, the condition resolved spontaneously without requiring chemotherapy. We monitored the neonate for a full year, during which no hematologic or developmental abnormalities were observed. Thirteen previous cases of neonates with TAM but without the DS phenotype have been reported. During the onset of TAM, the presence of trisomy 21 can be detected in peripheral blood cells or bone marrow cells, but some patients may not show evidence of trisomy 21 in fibroblasts. In these patients, trisomy 21 in peripheral blood cells or bone marrow cells may gradually decrease and even disappear as TAM improves. All patients experienced self-limiting remission with a favorable prognosis, although one case progressed to myeloid leukemia associated with DS by age two.

A negative obstetrical diagnosis and the absence of clinical DS phenotype should not preclude the consideration of TAM in neonates, especially when trisomy 21 mutations are detected.