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DDX41-related hematologic malignancy predisposition syndrome(MPLPF)

MedGen UID:
Concept ID:
Synonym: Myeloproliferative/lymphoproliferative neoplasms, familial (multiple types), susceptibility to
Modes of inheritance:
Non-Mendelian inheritance
MedGen UID:
Concept ID:
Genetic Function
Source: Orphanet
A mode of inheritance that depends on genetic determinants in more than one gene.
Gene (location): DDX41 (5q35.3)
Monarch Initiative: MONDO:0014809
OMIM®: 616871
Orphanet: ORPHA488647

Disease characteristics

DDX41-associated familial myelodysplastic syndrome and acute myeloid leukemia (MDS/AML) is characterized by an increased risk of myeloid neoplasms, lymphoid neoplasms, adult-onset single- or multiple-lineage cytopenias (including aplastic anemia), and red blood cell macrocytosis. The most common myeloid neoplasms include MDS, AML, and therapy-related myeloid neoplasms. Chronic myelomonocytic leukemia, chronic myeloid leukemia, and myeloproliferative neoplasms are less common. Lymphoid neoplasms include non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia. [from GeneReviews]
Jane E Churpek  |  Kelcy Smith-Simmer   view full author information

Additional description

Familial myeloproliferative/lymphoproliferative neoplasms (MPLPF) is an autosomal dominant cancer predisposition syndrome characterized by adult-onset of hematologic malignancies mainly affecting the myeloid line. Most patients present with myelodysplastic syndrome (MDS; 614286) and/or acute myeloid leukemia (AML; 601626). Rare lymphoid malignancies, including lymphoma, can also occur. Some mutation carriers, even if unaffected by a hematologic malignancy, may have evidence of immune dysregulation disorders, including asthma, eczema, or juvenile arthritis. The disorder shows incomplete penetrance (summary by Lewinsohn et al., 2016). Patients may show a favorable response to treatment with lenalidomide (summary by Polprasert et al., 2015).  http://www.omim.org/entry/616871

Clinical features

From HPO
Acute myeloid leukemia
MedGen UID:
Concept ID:
Neoplastic Process
A clonal expansion of myeloid blasts in the bone marrow, blood or other tissues. The classification of acute myeloid leukemias (AMLs) encompasses four major categories: 1) AML with recurrent genetic abnormalities; 2) AML with multilineage dysplasia; 3) Therapy-related AML; 4) AML not otherwise specified. The required bone marrow or peripheral blood blast percentage for the diagnosis of AML is 20% (WHO classification)
MedGen UID:
Concept ID:
Neoplastic Process
A cancer originating in lymphocytes and presenting as a solid tumor of lymhpoid cells.
MedGen UID:
Concept ID:
Congenital Abnormality
Clonal hematopoietic stem cell disorders characterized by dysplasia (ineffective production) in one or more hematopoietic cell lineages, leading to anemia and cytopenia.
Refractory anemia
MedGen UID:
Concept ID:
Disease or Syndrome
A myelodysplastic syndrome characterized mainly by dysplasia of the erythroid series. Refractory anemia is uncommon. It is primarily a disease of older adults. The median survival exceeds 5 years. (WHO, 2001)
Bone marrow hypocellularity
MedGen UID:
Concept ID:
A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat.
Erythroid dysplasia
MedGen UID:
Concept ID:
Dysplasia in the erythroid lineage, which presents with a variety of morphological changes in the bone marrow, including nuclear budding or irregular nuclear contour in erythroblasts.
MedGen UID:
Concept ID:
Disease or Syndrome
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
Eczematoid dermatitis
MedGen UID:
Concept ID:
Disease or Syndrome
Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.
MedGen UID:
Concept ID:
Disease or Syndrome
An abnormal decreased number of leukocytes in the blood.
Systemic lupus erythematosus
MedGen UID:
Concept ID:
Disease or Syndrome
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by production of autoantibodies against nuclear, cytoplasmic, and cell surface molecules that transcend organ-specific boundaries. Tissue deposition of antibodies or immune complexes induces inflammation and subsequent injury of multiple organs and finally results in clinical manifestations of SLE, including glomerulonephritis, dermatitis, thrombosis, vasculitis, seizures, and arthritis. Evidence strongly suggests the involvement of genetic components in SLE susceptibility (summary by Oishi et al., 2008). Genetic Heterogeneity of Systemic Lupus Erythematosus An autosomal recessive form of systemic lupus erythematosus (SLEB16; 614420) is caused by mutation in the DNASE1L3 gene (602244) on chromosome 3p14.3. An X-linked dominant form of SLE (SLEB17; 301080) is caused by heterozygous mutation in the TLR7 gene (300365) on chromosome Xp22. See MAPPING and MOLECULAR GENETICS sections for a discussion of genetic heterogeneity of susceptibility to SLE.
MedGen UID:
Concept ID:
Disease or Syndrome
An increased number of circulating monocytes.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDDX41-related hematologic malignancy predisposition syndrome

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