ABSTRACT
Monosomy 7 (loss of chromosome 7) along with interstitial (partial) deletion of the long arm of chromosome 7 [del(7q)] is a genetic disorder that typically manifests as early-childhood onset bone marrow insufficiency/failure and predisposition to hematologic malignancies (particularly MDS and AML). Familial monosomy 7 syndrome tends to involve 2 or more individuals in a family whereas monosomy 7 affects only one in a family. The pathogenesis of monosomy 7 or del(7q) is attributed to haploinsufficiency that results from the deletion of several important genes (eg, SAMD9, SAMD9L, EZH2 and MLL3) within chromosome 7. Specifically, loss of chromosome 7 in hematopoietic stem and progenitor cells (HSPC) at an early stage followed by deletion of SAMD9/SAMD9L puts these cells in an advantaged position over the surrounding cells for further expansion and transformation into MDS. Alternatively, HSPC with existing abnormal or even leukemic changes is disturbed by subsequent monosomy 7 and loss of EZH2 and/or MLL3, leading to myeloid tumorigenesis. Diagnosis of familial monosomy 7 syndrome involves medical history review, physical exam, and cytogenetic/molecular analysis. Bone marrow transplantation (allogeneic stem cell transplantation) represents a curative treatment for myeloid leukemia linked to monosomy 7 or del(7q).
