Am J Med Genet A. 2025 Feb 24:e63979. doi: 10.1002/ajmg.a.63979. Online ahead of print.
ABSTRACT
Transient abnormal myelopoiesis (TAM) is a transitory, myeloproliferative condition nearly exclusively present in infants with complete trisomy 21 (T21), or in its rare form, T21 mosaicism. We present here a case study of a neonate diagnosed with T21 mosaicism and TAM who did not exhibit the typical phenotypic features of down syndrome (DS), but displayed hematologic abnormalities, in addition to hepatosplenomegaly. Initial genetic testing suggested acute myeloid leukemia (AML) but subsequent evaluations were indicative of T21 mosaicism confined to the myeloid cell line, with negative results from lymphocytes cultured from a skin biopsy. A pathogenic GATA1 variant was found in the bone marrow in addition to three copies of RUNX1, associated with aberrant hematopoiesis in TAM. The infant responded to a brief course of chemotherapy and demonstrated normal growth and development at four years of age. In addition to this case, we identified 25 cases from the literature of mosaic T21 restricted to the myeloid cell line supporting normal development following treatment for TAM. As this case and the literature review demonstrate, T21 mosaicism apparently isolated to the bone marrow is unlikely to be associated with systemic or neurodevelopmental manifestations of DS.
PMID:39995092 | DOI:10.1002/ajmg.a.63979
