First case of neutropenia and thrombocytopenia in the setting of cerebral cavernous malformation 3
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Cerebral cavernous malformation 3 (CCM3) is a vascular malformation disorder causing brain slow-flow vascular parenchymal lesions. These lesions are the result of variants in the Programmed Cell Death Protein 10 (PDCD10) gene, located on 3q26.1. We report an 8-month-old patient who was presented with seizures and intracranial abscesses and was found to have a variant of PDCD10 on whole exome sequencing, representing, to our knowledge, the youngest case of CCM3 described in the literature. Her clinical course was complicated by the development of neutropenia, requiring granulocyte colony-stimulating factor, and thrombocytopenia, requiring intermittent platelet transfusions, with later development of B acute lymphoblastic leukemia 2 years after initial presentation. This case represents the first description in the literature of hematologic complications in the setting of CCM3. We hypothesize that these hematological manifestations are the result of alterations in the actin and microtubule cytoskeleton, affecting the process of hematopoiesis in a similar fashion to the documented effect of the PDCD10 variant on neuronal migration.
KeywordsCerebral cavernous malformation 3 Neutropenia Thrombocytopenia Pancytopenia Vascular malformation
The authors are grateful to the patient and her family as well as the clinical staff at Texas Children’s Hospital Hematology and Cancer Centers for their participation.
C. T. Cohen and K. L. Bergstrom prepared the initial draft of the manuscript. Revision and editing of the manuscript were done by C. T. Cohen, K. L. Bergstrom, G. Sasa, M. T. Elghetany, R. Xiao, and I. Iacobas.
Compliance with ethical standards
Conflict of interest
C. T. Cohen has research funding from Bayer Consumer Care AG, unrelated to above case report. R. Xiao works in the Department of Molecular and Human Genetics at Baylor College of Medicine which receives revenue from clinical genetic testing done at Baylor Genetics. K. L. Bergstrom, M. T. Elghetany, G. Sasa, and I. Iacobas declare that they have no conflict of interest.
The patient’s parents have provided verbal consent for participation in this publication. This report was reviewed by the Baylor College of Medicine institutional review board and deemed exempt from review.
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