Prenatal diagnosis of Down syndrome combined with transient abnormal myelopoiesis in foetuses with a GATA1 gene variant: Two case reports

Background: Transient abnormal myelopoiesis (TAM) is a transient haematological disorder of Down syndrome that is characterised by leucocytosis, the presence of blasts, abnormal haematopoiesis and hepatosplenomegaly. It is usually diagnosed within 8 weeks of birth, and the median age of diagnosis is 3–7 days. Case presentation We report two cases of prenatally diagnosed TAM, both with male foetal onset. One case was a rare placental low percentage 21 trisomy mosiacism, resulting in the occurrence of a false negative NIPT. The final diagnosis was made at 36 weeks of gestation when ultrasound revealed significant enlargement of the foetal liver and spleen and an enlarged heart; the foetus eventually died in utero. We detected a placenta with a low percentage (5%-8%) of trisomy 21 mosiacism by CNV-seq and FISH. In another case, foetal oedema was detected by ultrasound at 31 weeks of gestation. Two foetuses were diagnosed with Down syndrome by chromosomal microarray analysis (CMA) via umbilical vein puncture and had significantly elevated cord blood leucocyte counts with large numbers of blasts. The GATA1 Sanger sequencing results suggested the presence of a [NM_002049.4( GATA1 ):c.220G > A (p. Val74Ile)] hemizygous variant and a [NM_002049.4( GATA1 ):c.49dupC(p. Gln17ProfsTer23)] hemizygous variant of the GATA1 gene in two cases. Conclusion It seems highly likely that these two identified mutations are the genetic cause of prenatal TAM in foetuses with Down syndrome.