Clinical characteristics: ANKRD26-related thrombocytopenia is characterized by lifelong mild-to-moderate thrombocytopenia with a normal platelet size and no syndromic associations. Most individuals have normal hemostasis or a mild bleeding phenotype and do not develop severe spontaneous bleeding. Some individuals may have concomitant erythrocytosis and leukocytosis. The risk for myeloid malignancies (including myelodysplastic syndrome, acute myelogenous leukemia, and chronic myelogenous leukemia) is increased in individuals with ANKRD26 pathogenic variants.
Diagnosis/testing: The diagnosis of ANKRD26-related thrombocytopenia is established in a proband by the presence of lifelong thrombocytopenia and identification of a heterozygous pathogenic variant in ANKRD26 on molecular genetic testing.
Management: Treatment of manifestations: Adjunct hemostatic agents (e.g., antifibrinolytics, desmopressin) for bleeding or a major surgical procedure; platelet transfusions are reserved for severe bleeding or procedures with a high bleeding risk.
Prevention of secondary complications: For individuals with a myeloid neoplasm, careful consideration of stem cell transplant eligibility and pre-transplant therapies undertaken through a large academic institution with experience in the management of individuals with germline predisposition syndromes.
Surveillance: Surveillance for early detection of myeloid neoplasms should include an annual complete blood count with bone marrow examination if abnormalities are noted.
Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual by evaluation of the platelet count and molecular genetic testing of the ANKRD26 pathogenic variant in the family in order to identify as early as possible those who may benefit from surveillance.
Genetic counseling: ANKRD26-related thrombocytopenia is inherited in an autosomal dominant manner. All individuals reported to date have an affected parent. Each child of an individual with ANKRD26-related thrombocytopenia has a 50% chance of inheriting the ANKRD26 pathogenic variant. Once the ANKRD26 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible; however, phenotypic variability (due to variable expressivity) within families is observed.
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