# Germline predisposition to myeloid neoplasms (inherited predisposition to AML and MDS)

Source: https://onco.cc/terms/germline-myeloid-predisposition/  
OnCo record `germline-myeloid-predisposition` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Some people are born with a gene change that raises their risk of myelodysplastic syndrome or acute myeloid leukaemia, through genes such as DDX41, RUNX1, GATA2 and CEBPA or bone marrow failure conditions. Testing matters because it changes surveillance, treatment and which relative can safely donate stem cells.

## Summary

The WHO (2022) and the International Consensus Classification recognise myeloid neoplasms with germline predisposition. The AACR 2024 update groups the predispositions by the risk of MDS: without other organ dysfunction (DDX41, RUNX1, ANKRD26, ETV6), with organ dysfunction (GATA2 deficiency with at least 80% lifetime MDS/AML penetrance, SAMD9/SAMD9L), and bone marrow failure syndromes (Fanconi anaemia, Shwachman-Diamond syndrome, telomere biology disorders, severe congenital neutropenia, Diamond-Blackfan anaemia). CEBPA and PAX5 predispose to acute leukaemia without a risk of MDS.

General advice for all: at least annual examination, education about symptoms, care at a centre with expertise, early consultation with a transplant specialist, a baseline blood count and, for those at risk of MDS in childhood, a baseline marrow. For syndromes with prognostic data, serial somatic gene panels on marrow detect clonal evolution (TP53 in Shwachman-Diamond syndrome, monosomy 7 with SETBP1, ASXL1 or RUNX1 in GATA2 deficiency). NCCN recommends predisposition testing in all patients with MDS and adults under 50 with AML; related donors are tested.

## Fields

- Kind: Term
- Last checked: 2026-11-04
- Also known as: inherited predisposition to acute myeloid leukaemia; hereditary myeloid malignancy; haematopoietic malignancy predisposition; myeloid neoplasms with germline predisposition; familial AML
- Tags: gap-fill; hereditary

## Notes

- NHS England genomic test directory: R347, inherited predisposition to acute myeloid leukaemia (AML).

## Sources

- Maese, Clin Cancer Res 2024: surveillance for children with predisposition to haematopoietic malignancy (AACR update): https://doi.org/10.1158/1078-0432.ccr-24-0685
- NHS England National Genomic Test Directory, rare and inherited disease, version 9 (spreadsheet): https://www.england.nhs.uk/wp-content/uploads/2018/08/rare-and-inherited-disease-national-genomics-test-directory-v9.xlsx

## Connected records

- terms: [DDX41-associated predisposition to myeloid neoplasms](https://onco.cc/terms/ddx41-myeloid-predisposition/), [Dyskeratosis congenita and telomere biology disorders](https://onco.cc/terms/dyskeratosis-congenita/), [Fanconi anaemia](https://onco.cc/terms/fanconi-anaemia/), [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/), [RUNX1 familial platelet disorder with associated myeloid malignancy](https://onco.cc/terms/familial-platelet-disorder-runx1/), [Shwachman-Diamond syndrome](https://onco.cc/terms/shwachman-diamond-syndrome/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Myelodysplastic syndromes / neoplasms (MDS)](https://onco.cc/cancers/mds/)
- technologies: [Allogeneic stem cell transplantation](https://onco.cc/technologies/allogeneic-hsct/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/)
- targets: [CEBPA](https://onco.cc/targets/cebpa/), [DDX41](https://onco.cc/targets/ddx41/), [ETV6](https://onco.cc/targets/etv6/), [GATA2](https://onco.cc/targets/gata2/), [RUNX1](https://onco.cc/targets/runx1/)
- drugs: [CancerNext and CancerNext-Expanded (Ambry Genetics)](https://onco.cc/drugs/ambry-cancernext/)

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