GENETIC TESTING FOR FAMILIAL THROMBOCYTOPENIA – THE PROS AND CONS SHORT TITLE: GENETIC TESTING IN THROMBOCYTOPENIA
- 1The Hospital for Sick Children, Canada
Abstract
Introduction: Thrombocytopenia, defined as a platelet count < 150 × 109/L is one of the most common cytopenias in children. Thrombocytopenia can be acquired (e.g., ITP) or familial, with the latter often being misdiagnosed as ITP, resulting in inappropriate, and potentially risky and ineffective, treatments. Recently, there has been an increase in the use of genetic testing to identify the cause of familial thrombocytopenia, which has the potential to avoid misdiagnosis and patient exposure to ineffective treatments. This has increased the volume of genetic information, which has created challenges in the accurate assessment and reporting of variants. One concerning aspect is the detection in thrombocytopenia patients of variants in the known cancer predisposing genes: RUNX1, ETV6, and ANKRD26. Detection of cancer predisposing gene variants can cause considerable anxiety, especially in cases where it has not been established whether the particular variant is pathogenic, benign or of unknown significance (i.e. VUS). Objectives: We performed a retrospective study of pediatric patients with thrombocytopenia referred/followed at our Comprehensive Bleeding Disorders Clinic who underwent genetic testing and were found to have genetic variants associated with thrombocytopenia. Specifically, we wanted to highlight variants in RUNX1, ETV6, and ANKRD26 genes. Methods: A retrospective chart review of pediatric patients with familial thrombocytopenia referred to our outpatient Comprehensive Bleeding Disorders Clinic at The Hospital for Sick Children, Toronto, Canada was conducted. Results: 102 pediatric patients with familial thrombocytopenia were found to have variants associated with thrombocytopenia: 74 had only one variant, while 28 had 2 or 3 identified variants. Our patients were differentiated according to platelet size among macrothrombocytopenias, normal sized thrombocytopenias and microthrombocytopenias. Macrothrombocytopenias were the most common form of familial thrombocytopenias, accounting for 82 (80.3%) of the 102 patients found to have a thrombocytopenia causative genetic variant. Of these, MYH9 variants were the most common including 25 patients (30.4%). Except for Bernard Soulier and Gray platelet syndromes, all other macrothrombocytopenias are inherited in an autosomal dominant fashion. Seventeen patients with normal sized platelets had variants in a cancer predisposing gene (RUNX1, ANKRD26, or ETV6). All 5 RUNX variants were reported as pathogenic while the 8 ANKRD26 and 4 ETV variants were all described as VUSs. Only 3 patients (2.9%) were identified to have variants related to microthromobocytopenias. Conclusion: Genetic testing can contribute to the precise diagnosis of thrombocytopenia. In our cohort, patients with normal sized platelets showed a high incidence of variants in RUNX1, ANKRD26, and ETV6, with the RUNX1 variants predicted to be pathogenic, while the others were of unknown significance. The detection of these cancer predisposing genes needs to be considered when getting initial genetic consent from parents/patients to minimize the resulting potential anxiety and to manage patient/family counselling.
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BibTeX
@article{souza2026genetic,
title = {{GENETIC TESTING FOR FAMILIAL THROMBOCYTOPENIA – THE PROS AND CONS SHORT TITLE: GENETIC TESTING IN THROMBOCYTOPENIA}},
author = {Lara LOBIANCO E SOUZA and Cindy Wakefield WAKEFIELD and Shree KONERU and Walter KAHR and Caroline MALCOLMSON and Vanessa BOUSKILL and Margaret Lucille RAND and Manuel CARCAO},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.108363},
url = {https://doi.org/10.1016/j.htct.2026.108363},
note = {CC BY},
}
RIS
TY - JOUR
TI - GENETIC TESTING FOR FAMILIAL THROMBOCYTOPENIA – THE PROS AND CONS SHORT TITLE: GENETIC TESTING IN THROMBOCYTOPENIA
AU - Lara LOBIANCO E SOUZA
AU - Cindy Wakefield WAKEFIELD
AU - Shree KONERU
AU - Walter KAHR
AU - Caroline MALCOLMSON
AU - Vanessa BOUSKILL
AU - Margaret Lucille RAND
AU - Manuel CARCAO
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.108363
UR - https://doi.org/10.1016/j.htct.2026.108363
AB - Introduction: Thrombocytopenia, defined as a platelet count < 150 × 109/L is one of the most common cytopenias in children. Thrombocytopenia can be acquired (e.g., ITP) or familial, with the latter often being misdiagnosed as ITP, resulting in inappropriate, and potentially risky and ineffective, treatments. Recently, there has been an increase in the use of genetic testing to identify the cause of familial thrombocytopenia, which has the potential to avoid misdiagnosis and patient exposure to ineffective treatments. This has increased the volume of genetic information, which has created challenges in the accurate assessment and reporting of variants. One concerning aspect is the detection in thrombocytopenia patients of variants in the known cancer predisposing genes: RUNX1, ETV6, and ANKRD26. Detection of cancer predisposing gene variants can cause considerable anxiety, especially in cases where it has not been established whether the particular variant is pathogenic, benign or of unknown significance (i.e. VUS). Objectives: We performed a retrospective study of pediatric patients with thrombocytopenia referred/followed at our Comprehensive Bleeding Disorders Clinic who underwent genetic testing and were found to have genetic variants associated with thrombocytopenia. Specifically, we wanted to highlight variants in RUNX1, ETV6, and ANKRD26 genes. Methods: A retrospective chart review of pediatric patients with familial thrombocytopenia referred to our outpatient Comprehensive Bleeding Disorders Clinic at The Hospital for Sick Children, Toronto, Canada was conducted. Results: 102 pediatric patients with familial thrombocytopenia were found to have variants associated with thrombocytopenia: 74 had only one variant, while 28 had 2 or 3 identified variants. Our patients were differentiated according to platelet size among macrothrombocytopenias, normal sized thrombocytopenias and microthrombocytopenias. Macrothrombocytopenias were the most common form of familial thrombocytopenias, accounting for 82 (80.3%) of the 102 patients found to have a thrombocytopenia causative genetic variant. Of these, MYH9 variants were the most common including 25 patients (30.4%). Except for Bernard Soulier and Gray platelet syndromes, all other macrothrombocytopenias are inherited in an autosomal dominant fashion. Seventeen patients with normal sized platelets had variants in a cancer predisposing gene (RUNX1, ANKRD26, or ETV6). All 5 RUNX variants were reported as pathogenic while the 8 ANKRD26 and 4 ETV variants were all described as VUSs. Only 3 patients (2.9%) were identified to have variants related to microthromobocytopenias. Conclusion: Genetic testing can contribute to the precise diagnosis of thrombocytopenia. In our cohort, patients with normal sized platelets showed a high incidence of variants in RUNX1, ANKRD26, and ETV6, with the RUNX1 variants predicted to be pathogenic, while the others were of unknown significance. The detection of these cancer predisposing genes needs to be considered when getting initial genetic consent from parents/patients to minimize the resulting potential anxiety and to manage patient/family counselling.
SN - 2531-1379
SN - 2531-1387
ER -