NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.

Clinical characteristics: Familial monosomy 7 is characterized by early-childhood onset of bone marrow insufficiency/failure associated with increased risk for myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). In all reported individuals, the monosomy 7 is believed to be an acquired cytogenetic abnormality within hematopoietic cells due to as-yet poorly defined inherited genetic predisposition. Identification of peripheral blood leukocytes with monosomy 7 usually precedes bone marrow failure/MDS/AML by a few months to years. Nearly all individuals reported with familial monosomy 7 have died of their disease.

Note: Only a minority of individuals with bone marrow failure/MDS/AML with monosomy 7 have familial monosomy 7.

Diagnosis/testing: Detection of cells with monosomy 7 during evaluation of a hematologic abnormality or malignancy or in the context of chromosomal studies in the diagnosis of unrelated conditions needs to be confirmed with bone marrow cytogenetic and interphase FISH studies. A bone marrow karyotype of 45,XX,-7 in females or 45,XY,-7 in males, often mosaic with normal cells (i.e., 46,XX in females and 46,XY in males), confirms the presence of monosomy 7. Of note, individuals with a family history of monosomy 7 (e.g., an affected sib) may initially have a normal karyotype in peripheral blood and/or bone marrow and later transition to mosaic monosomy 7 in peripheral blood and/or bone marrow.

Management: Treatment of manifestations: Urgent referral to an oncologist should be considered for individuals with monosomy 7 (mosaic or non-mosaic). Definitive therapy is bone marrow transplantation (BMT) prior to the emergence of a leukemic clone. The suitability of sibs who are potential bone marrow donors may be evaluated with appropriate hematologic and cytogenetic studies to rule out bone marrow disease associated with familial monosomy 7. However, given that the underlying germline pathogenic variant may not be known, a matched sib donor may not be an ideal candidate (unless much older than the affected individual and with no evidence of hematologic disorders). An unrelated donor may be more suitable.

Prevention of secondary complications: It is unknown if the standard protocols for ablative therapy prior to BMT should be modified.

Surveillance: Annual monitoring of peripheral blood karyotype, hematologic status, and hemoglobin F levels helps identify emerging bone marrow abnormalities (cytopenias and bone marrow dysplasia) prior to the development of overt AML or MDS.

Evaluation of relatives at risk: In both children and adults with a family history of monosomy 7, otherwise unexplained signs and symptoms should be evaluated by a physician as possible early indications of the disorder.

Genetic counseling: The mode of inheritance of familial monosomy 7 is unknown.