More than just mild thrombocytopenia: Clinical clues in the diagnosis of germline predisposition to malignancy from a rare ETV6 variant

Abstract

Thrombocytopenia can be the first indication of an underlying condition in children and includes a wide range of differential diagnoses. Inherited thrombocytopenias are a heterogenous group of disorders with low platelet counts, with or without platelet dysfunction. With increasing access to genetic testing, the number of genes associated with this phenotype and number of patients diagnosed continue to grow. 1 Over 50 genes have been described to be associated with inherited thrombocytopenia and an estimated 2.7% are from disease-causing variants in ETS Variant Transcription Factor 6 (ETV6). 1,2 ETV6 is a transcription repressor in the ETS family of transcription factors, and it is implicated in normal hematopoiesis, thrombopoiesis, and platelet function. 3,4 Distinguishing ETV6-related thrombocytopenia (ETV6-RT) from other etiologies is important, given its associated risk of malignancy, 2-4 and requires genetic testing for diagnostic confirmation. This report describes the diagnostic approach and clinical challenges in a family with inherited thrombocytopenia that was found to carry a rare disease-causing ETV6 variant.