Inherited Thrombocytopenia Caused by Germline ANKRD26 Mutation Should Be Considered in Young Patients With Suspected Myelodysplastic Syndrome

Abstract

<jats:p> Thrombocytopenia 2 (THC2) is an autosomal dominant disorder characterized by ankyrin repeat domain 26 mutation and moderate thrombocytopenia. THC2 exposes patients to a low risk of bleeding and an increased likelihood of myelodysplastic syndrome/acute myeloid leukemia. Germline evaluation for a genetic disorder should be considered when a patient presents with isolated thrombocytopenia and associated dysmegakaryopoiesis. In this case report, we present a male patient who presented with isolated thrombocytopenia but was ultimately confirmed to have an inherited THC2 thrombocytopenia/myelodysplastic syndrome. Given the rarity of the disease, no clear guidelines on how to follow THC2 patients over the long term have been established. We recommend a monthly complete blood count and clinical visits every 3 months at a minimum. </jats:p>

Germline Predisposition to Myelodysplastic Syndromes

“…Carriers usually have moderate thrombocytopenia, normal-sized platelets, and an absent to mild bleeding predisposition with normal platelet aggregation studies. Typical bone marrow morphology demonstrates dysmegakaryopoiesis with hypolobulated megakaryocytes 36–38,43 . Thrombopoietin levels are typically elevated.…”

“…Germline mutations in the ankyrin repeat domain 26 gene ( ANKRD26 ), located on chromosome 10p12, are characterized by familial thrombocytopenia and an increased risk of myeloid malignancy 35–39 . Monoallelic mutations usually occur as single-nucleotide substitutions primarily in the 5′ untranslated region of the ANKRD26 gene and therefore can be missed on standard exome sequencing, which does not capture the ANKRD26 promoter sequence 35,37 .…”

Familial thrombocytopenia: The long and short of it

“…Inherited thrombocytopenia 2 (THC2) is an autosomal dominant disorder characterized by ankyrin repeat domain 26 ( ANKRD26 ) mutations, which cause aberrant ANKRD26 overexpression during megakaryocyte differentiation with consequent impaired platelet production and a predisposition to myeloid malignancies ( Noris et al, 2011 ; Pippucci et al, 2011 ). While THC2 is rare, distinguishing this condition from other noninherited causes of thrombocytopenia such as myelodysplasia ( Kewan et al, 2020 ) or immune thrombocytopenia is crucial. THC2 is typically caused by single nucleotide variants (SNVs) in the 5′ untranslated region of the ANKRD26 gene.…”