Transient Abnormal Myelopoeisis and Mosaic down Syndrome in a Phenotypically Normal Newborn

Abstract

Transient abnormal myelopoiesis (TAM) is a common and potentially fatal neonatal complication of newborn babies with Down syndrome (DS). Children born with mosaic DS are also at risk of developing TAM. However, due to their variable phenotypes, early identification of patients with mosaic DS may be difficult; thus, early diagnosis of TAM is just as challenging. In this report, we describe a case of a phenotypically normal newborn who presented with concerns for neonatal leukemia. The diagnosis of mosaic DS and TAM was confirmed with abnormal GATA1 mutation testing, highlighting the importance of early GATA1 mutation testing in newborn leukemia with high suspicion for TAM.

Cytogenetics of Pediatric Acute Myeloid Leukemia: A Review of the Current Knowledge

“…Finally, GATA1 mutations, which are characteristic of DS-AMKL, can also be found in 9% of non DS-AMKL; trisomy 21 is a constant feature in these cases, raising the possibility of constitutional mosaicism for trisomy 21, as demonstrated in 1/10 of these cases with available non-hematopoietic tissue [ 63 ]. Of note, similar findings have been reported in TAM occurring in phenotypically normal newborns, and thus suggests a search for constitutional trisomy 21 mosaicism in these cases [ 147 ].…”

Transient myeloproliferative disorder as the presenting feature for mosaic trisomy 21

“…There are other reports of newborns with TMD without other clinical features of Down syndrome who had mosaic trisomy 21 in blood and bone marrow at diagnosis ( Bhatt et al 1995 ; Rozen et al 2014 ; Prudowsky et al 2020 ). In some of these reports, the mosaicism persisted after the TMD had resolved ( Bhatt et al 1995 ), but in others, once the TMD has resolved, trisomy 21 could not be identified in the blood ( Rozen et al 2014 ; Prudowsky et al 2020 ).…”

Rapid next-generation sequencing aids in diagnosis of transient abnormal myelopoiesis in a phenotypically normal newborn

“…9 Neonates with T21 mosaicism are at risk for T21associated complications, such as TAM, in affected tissues, though recognition of this entity can be challenging in the absence of phenotypic features of DS. 7,8 In most cases, there is extinction of the abnormal myeloid clone early in infancy, and TAM selfresolves within months. 10 Cytoreductive treatment with leukapheresis or chemotherapy may be necessary in cases of life-threatening complications such as cardiorespiratory compromise, hyperleukocytosis, renal or liver dysfunction, disseminated intravascular coagulopathy, hydrops fetalis, or hyperviscosity.…”