Study of Individuals and Families With Aberrations in DDX41 or Similar Cancer Predisposition Variants

Background: Hereditary hematopoietic malignancy (HHM) syndromes are a group of inherited disorders that raises the risk of blood cancers. Many people with HHMs have changes in a gene (DDX41) that makes it more likely that they will develop myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), or other cancers. This natural history study will explore the link between HHM syndromes and these diseases. Objective: To study the link between HHM and MDS/AML. Eligibility: People aged 1 month and older with HHM. Relatives with HHM are also needed. Design: Participants aged 3 years and older will have 1 initial clinic visit with the option to follow-up annually. They will undergo these procedures: They will have a physical exam with blood and urine tests. They may give samples of saliva, stool, nails, and skin. Their ability to do normal activities will be reviewed. Some may have a bone marrow biopsy: A tissue sample will be drawn from inside a bone. They may answer questions about their health and family medical history. Participants younger than 3 years, and those who cannot come to the clinic, will be contacted by phone or email. Their samples may be collected locally and sent to researchers. For participants who have changes in their DDX41 gene: Researchers will contact them or their primary care provider once a year for 10 years. Researchers will check on participants health and collect any new test results. Some may be asked to send new samples. Participants who do not have changes in their DDX41 gene may be contacted yearly, or less often, for 10 years. Some participants may be asked to return to the clinic if needed.

Sex

All

Minimum age

1 Month

Maximum age

120 Years

* INCLUSION CRITERIA:
* Age \> 1 month old.
* Participants with history of aberrations that affect the DDX41 gene, DDX41 RNA, or DDX41 protein (Cohorts 1-2)

OR

Participants with history of aberrations in another HHM variant (Cohort 3)

OR

Participants with history of absence of HHM variants, who have first or second degree relative with history of confirmed or suspected HHM variant(s) per participant report (Cohort 4).

* Participants must have an identified healthcare provider outside of NIH who manages participant care, and any diagnostic clinical findings provided by this study.
* Ability of participant or parent/guardian to understand and the willingness to sign a written consent document.

EXCLUSION CRITERIA:

None.