{"id":27167,"date":"2024-05-26T15:57:37","date_gmt":"2024-05-26T13:57:37","guid":{"rendered":"https:\/\/www.krebs-praedisposition.de\/?post_type=kompendium&p=27167"},"modified":"2025-08-26T13:43:34","modified_gmt":"2025-08-26T11:43:34","slug":"runx1-deficiency","status":"publish","type":"kompendium","link":"https:\/\/www.krebs-praedisposition.de\/en\/kompendium\/runx1-deficiency\/","title":{"rendered":"RUNX1 Deficiency"},"content":{"rendered":"

RUNX1 Deficiency \u2013\u00a0Definition<\/h2><\/div>
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RUNX1 deficiency or familial platelet disorder with associated myeloid malignancy (FPDMM, OMIM #601399) is a genetic disease caused by pathogenic variants in the RUNX1<\/em> gene. Characteristic features include thrombocytopenia, thrombocytopathy with a prolonged bleeding time, and an increased risk of developing myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or acute T-cell leukemia (T-ALL). The clinical presentation is heterogeneous.<\/p>\n<\/div>

Synonym:<\/p>\n<\/div><\/div><\/div>

familial platelet disorder with associated myeloid malignancy (FPDMM)<\/p>\n<\/div><\/div><\/div><\/div>

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Gene:<\/p>\n<\/div><\/div><\/div>

RUNX1<\/i><\/p>\n<\/div><\/div><\/div><\/div>

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Gen\u00ade product:<\/p>\n<\/div><\/div><\/div>

RUNX1 (runt-related transcription factor 1) and<\/p>\n

AML1 (acute myeloid leukemia 1) and<\/p>\n

CBFA2 (core-binding factor subunit alpha-2)<\/p>\n<\/div><\/div><\/div><\/div>

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Function:<\/p>\n<\/div><\/div><\/div>

Transcription factor that regulates the differentiation of hematopoietic cells in adult stem cells<\/p>\n<\/div><\/div><\/div><\/div>

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Pattern of inheritance:<\/p>\n<\/div><\/div><\/div>

Autosomal dominant<\/p>\n<\/div><\/div><\/div><\/div>

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Prevalence:<\/p>\n<\/div><\/div><\/div>

Unknown<\/p>\n<\/div><\/div><\/div><\/div>

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Genotype-phenotype correlation:<\/p>\n<\/div><\/div><\/div>

Not clear.
\nPathogenic variants with a dominant negative effect (missense mutations in the RUNT homology domain, nonsense and frameshift mutations in the C-terminal domain) exhibit an increased risk of MDS\/AML.
\nDeletions may be associated with a syndromic phenotype (contiguous gene syndrome).<\/p>\n<\/div><\/div><\/div><\/div>

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Penetrance:<\/p>\n<\/div><\/div><\/div>

Very variable overall, 30-40% for MDS\/AML<\/p>\n<\/div><\/div><\/div><\/div><\/div><\/div>

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Overview of the Chapters on This Page:<\/h4><\/div><\/div><\/div>