Myelodysplastic Syndrome with Monosomy 7 in a Patient with Ataxia-Pancytopenia Syndrome

Abstract Introduction/Objective Ataxia-pancytopenia syndrome is caused by mutations in SAMD9L, a tumor suppressor gene on chromosome 7 with roles in normal hematopoiesis and cerebellar development. Syndrome manifestations consist of a combination of progressive ataxia, multilineage cytopenias, and increased risk of myeloid neoplasms associated with monosomy 7. Histopathologic and radiologic descriptions of this recently described disorder are scarce and treatment strategies are not standardized. Additionally, features that predict spontaneous hematologic remission of myeloid neoplasms are incompletely understood. Therefore, detailed discussions of this disorder and its possible outcomes are warranted. Methods/Case Report A six-year-old boy was brought to his doctor when his parents noticed head tilting while reading and impaired coordination. Brain MRI revealed extensive T2/FLAIR hyperintensities of white matter, cerebellar hypoplasia, and a thinned corpus callosum. Further evaluation excluded autoimmune etiologies, infectious diseases, and inherited leukodystrophies. Whole exome sequencing demonstrated a previously uncharacterized heterozygous mutation in SAMD9L, c.2062T>A; p.Tyr688Asn. Subsequent testing revealed pancytopenia. A bone marrow biopsy showed small megakaryocytes with abnormal nuclear lobation and erythroid progenitors with nuclear blebbing and binucleation. Blasts were borderline increased (4%). Fluorescence in-situ hybridization and karyotype showed monosomy 7. A myeloid next-generation sequencing panel identified an ETV6 mutation (p.Gln143Ter, VAF=5.4%). A diagnosis of myelodysplastic syndrome with monosomy 7 in the setting of ataxia-pancytopenia syndrome was rendered. The patient underwent allogeneic stem cell transplant and is doing well at last follow-up. Results (if a Case Study enter NA) N/A Conclusion Ataxia pancytopenia syndrome is a recently described and incompletely understood disorder. Some myeloid neoplasms in ataxia-pancytopenia syndrome can undergo somatic revertant mosaicism via uniparental disomy, resulting in spontaneous hematologic remission. Factors that predict spontaneous remission are unclear; however, secondary mutations have been associated with poorer outcomes. This case emphasizes the value of comprehensive genetic testing modalities in challenging cases. Screening for SAMD9L mutations in cases of pediatric myelodysplastic syndrome could be considered.