Overview
There are many haematological conditions that affect children with Down Syndrome (DS) – ranging from non-specific changes in the blood count at birth, to malignant changes associated with leukaemia.
Children with DS have a > 50-fold increased risk of developing acute leukaemia before their 5th birthday compared to children without DS – population based studies show an increased frequency of both acute myeloid leukaemia and acute lymphoblastic leukaemia (Neha Bhatnagar 2023). This increased risk of Trisomy 21 associated leukaemias has been attributed to an imbalance of the RUNX1a gene and its interplay with point mutations of the GATA1 haematopoietic transcription factor.
In the newborn period, blood cell morphology and blood counts differ from those in babies without Down Syndrome (See “DSMIG Neonatal Guidelines: Best Practice Guidance” Rebecca Ferris 2018) e.g. haemoglobin and haematocrit are higher in babies with Down syndrome and ~20% are polycythaemic (haematocrit >0.65) and platelet counts may be lower than expected. The contribution of co-existing congenital heart disease, potential sepsis or intra-uterine growth restriction should be considered, but it is important to correlate blood results clinically and to reference the published haematological reference ranges specific to children with Down Syndrome.
Transient Abnormal Myelopoiesis (TAM) also known as Transient Leukaemia of Down Syndrome (TL- DS) is the most clinically important haematological disorder in the neonatal period. TAM is a disorder of foetal haematopoiesis in the liver and affects 10-30% of babies with DS. TAM may be asymptomatic (10-30%) but can present with severe disease (5-23%) e.g. organomegaly, cholestasis and hepatopathy, ascites, skin rash, pericardial and pleural effusions. Most cases present in the first 5 days of life, and therefore all newborns should have a FBC and film completed by Day 3 of life. If the peripheral blood (PB) blast cell percentage is >10%, a sample should be sent for GATA1 mutational analysis with an urgent discussion with the regional Paediatric Oncology Principal Treatment Centre. Chemotherapy with cytarabine may be considered for severe disease.
80% of babies with TAM will go into spontaneous remission, but 10-20% will later develop Myeloid Leukaemia of Down Syndrome (ML-DS) with a peak incidence at around 2 years of age. ML-DS is very chemosensitive with a 5 year survival of <90% – unlike the myeloid leukaemia seen in children who do not have DS.
Acute Lymphoblastic Leukaemia of Down Syndrome (ALL-DS) has clinical and haematological features that are similar to non-DS-ALL. However, there are poorer outcomes for children with ALL-DS– mainly due to treatment toxicity. Survival after relapse is also poor even after Bone Marrow Transplantation.
Dr Vicky Ho, March 2025
DSMIG Guidance
DSMIG Neonatal Guidelines Rebecca Ferris, updated September 2018 Neonatal Guidelines
A study of the neonatal haematology of children with Down syndrome. James R (2011)
Presentations at DSMIG Meetings
Presentation at DSMIG Academic Meeting, Royal Society of Medicine November 2024:
Common Haematological Conditions in Down Syndrome, Dr Neha Bhatnagar, Paediatric Haematology Consultant, Oxford DSMIG Winter Conference Nov 2023. This presentation is available to DSMIG members only who will need to log in to access them. For details on how to become a member click here.
Additional Resources
Guidelines for the investigation and management of Transient Leukaemia of Down Syndrome. Tunstall, O. , Bhatnagar, N. , James, B. , Norton, A. , O’Marcaigh, A. S., Watts, T. , Greenough, A. , Vyas, P. , Roberts, I. , Wright, M. and , (2018), British Journal of Haematology, 182: 200-211. last accessed 12 March 2025 – free access
RUNX1 isoform disequilibrium promotes the development of trisomy 21–associated myeloid leukemia | Blood | American Society of Hematology Gialesaki et al., Blood(2023) 141 (10): 1105–1118. https://doi.org/10.1182/blood.2022017619
Haematology of Down syndrome – David Webb, Irene Roberts and Paresh Vyas
Arch Dis Child Fetal Neonatal Ed 2007;92:F503–F507. doi: 10.1136/adc.2006.104638
Down Syndrome Personal Child Health Record Down Syndrome 2020.
A study of the neonatal haematology of children with Down syndrome. James R (2011)
Hematological studies in children with Down syndrome. David O, Fiorucci CC, Tosi MT, Altare F, Valori F, Saracco P, Asinardi P, Ramenghi U, Cabutti V 1996. . Pediatric Hematology and Oncology, 13(3), pp.271–275