Fatal transient abnormal myelopoiesis in a phenotypically normal neonate with mosaic Down syndrome: a case report highlighting diagnostic challenges and clinical implications

Abstract Background Down syndrome (DS), a prevalent chromosomal disorder, is generally characterized by distinctive facial features and congenital anomalies. Transient abnormal myelopoiesis (TAM) is a transient myeloproliferative disorder that occurs almost exclusively in neonates with DS. However, in mosaic DS, the lack of characteristic DS phenotypes poses a substantial diagnostic challenge. This difficulty is further compounded when TAM itself presents atypically, frequently leading to misdiagnosis. Case presentation We present a Chinese male neonate with mosaic DS (47, XY, + 21(mos, ~ 50%)) who developed rapidly progressive hemorrhagic ascites, disseminated intravascular coagulation, and multisystem organ collapse within hours of birth. Despite intensive resuscitation, the neonate died shortly after birth. Autopsy revealed extensive perisinusoidal hepatic fibrosis, multisystem extramedullary hematopoiesis (EMH), and megakaryocytic aggregation, which were characteristic of TAM. Conclusion This case highlights the critical diagnostic challenges posed by mosaic DS in phenotypically normal neonates. It underscores the importance of maintaining a high index of suspicion for TAM when encountering unexplained neonatal coagulopathy or effusions, as early recognition can guide clinical management and facilitate informed palliative care discussions.