Clinical Guidance

No clinically relevant genotype-phenotype correlations have been identified.

Source: GeneReviews — "ETV6-Related Thrombocytopenia and Predisposition to Leukemia"

Penetrance

The penetrance of thrombocytopenia in this disorder is thought to exceed 90%. The penetrance of malignancy, specifically lymphoid and myeloid, is estimated at 20%-30%.

Source: GeneReviews — "ETV6-Related Thrombocytopenia and Predisposition to Leukemia"

Diagnostic Criteria

ETV6-related thrombocytopenia and predisposition to leukemia is a nonsyndromic genetic disorder of thrombocytopenia and high risk of leukemia without any other consistent congenital anomalies. Formal clinical diagnostic criteria have not been published.

Suggestive Findings

ETV6-related thrombocytopenia and predisposition to leukemia should be considered in individuals with the following clinical and laboratory findings and family history.

Clinical findings

Source: GeneReviews — "ETV6-Related Thrombocytopenia and Predisposition to Leukemia"

Differential Diagnosis

Hereditary platelet disorders with increased leukemia risk to consider in the differential diangosis of ETV6-related thrombocytopenia and predisposition to leukemia are listed in .

Table 2.

Genes of Interest in the Differential Diagnosis of ETV6-Related Thrombocytopenia and Predisposition to Leukemia

Gene | Disorder | MOI | Associated Malignancies | Hematologic Findings

ANKRD26

| ANKRD26-related thrombocytopenia | AD | Myeloid malignancies (incl myelodysplastic syndrome, acute myelogenous leukemia, chronic myelogenous leukemia) | Mild-to-moderate thrombocytopenia w/normal platelet size

RUNX1

| RUNX1 familial platelet disorder/ acute myeloid leukemia | AD | • Myeloid malignancies are most common, incl acute myelogenous leukemia myelodysplastic syndrome.

Source: GeneReviews — "ETV6-Related Thrombocytopenia and Predisposition to Leukemia"

Management Guidelines

Expert and consensus clinical guidelines for the management of inherited thrombocytopenia and leukemia predisposition syndromes, including those with germline ETV6 pathogenic variants, have been proposed .

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with ETV6-related thrombocytopenia and predisposition to leukemia, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 3.

ETV6-Related Thrombocytopenia and Predisposition to Leukemia: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Hematologic/

Oncologic

| CBC w/differential | Incl peripheral smear for detection of hematologic neoplasms

Consider platelet aggregation studies. | If available platelet count allows

Consider bone marrow biopsy aspirate. | Assess baseline cellularity, morphology, cytogenetics.1

Consider referral to hematologist/oncologist. | Consider referral to center w/expertise in predisposition to malignancy; multidisciplinary team may help refine optimal mgmt.

Genetic counseling

| By genetics professionals,2 ideally in center w/experience in predisposition to hematologic malignancy | To obtain a pedigree inform affected persons their families re nature, MOI, implications of ETV6-related thrombocytopenia predisposition to leukemia to facilitate medical personal decision making

CBC = complete blood count; MOI = mode of inheritance

Source: GeneReviews — "ETV6-Related Thrombocytopenia and Predisposition to Leukemia"

Clinical Guidance

For individuals with ETV6-related thrombocytopenia and predisposition to leukemia and a history of bleeding, medications that decrease platelet function (e.g., aspirin, nonsteroidal anti-inflammatory drugs) should be avoided. Similarly, participation in contact sports is not recommended.

Source: GeneReviews — "ETV6-Related Thrombocytopenia and Predisposition to Leukemia"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "ETV6-Related Thrombocytopenia and Predisposition to Leukemia"

Surveillance Guidelines

Individuals with ETV6-related thrombocytopenia and predisposition to leukemia should adhere to published population-based cancer screening guidelines, including for breast and colon cancers. In addition to education regarding the signs and symptoms of hematologic malignancies, the following surveillance should be considered.

Table 5.

ETV6-Related Thrombocytopenia and Predisposition to Leukemia: Recommended Surveillance

System/Concern | Evaluation | Frequency

Hematology/

Oncology

| CBC w/differential | Every 6 to 12 mos1,2,3

Bone marrow aspirate biopsy4 | Every 1-3 yrs1,2

CBC = complete blood count

1. The benefit of this screening regimen is currently unknown.

2. The frequency of such screening must be weighed against the burden of the screening protocol, particularly in young children. The frequency of CBC and bone marrow evaluations should be determined on a case-by-case basis by the physician and with consideration of patient/family preferences.

3. If changes in the CBC with differential are persistent for two to fou weeks, particularly cytopenias, consider an additional bone marrow aspirate and biopsy.

4. To include morphology, cytogenetics, fluorescence in situ hybridization (FISH) (e.g., for chromosomes 5q, 7q, 8, and 20q), and molecular studies (depending on morphology, cytogenetics, and/or FISH)

Source: GeneReviews — "ETV6-Related Thrombocytopenia and Predisposition to Leukemia"