American Journal of Medical Genetics 35:437-441 (1990) z -~ ~ ~~~~ ~~~ Myelodysplasia and Leukemia Syndrome With Monosomy 7: A zyxw Genetic Perspective D.M. Gilchrist, J.M. Friedman, P.C.J. Rogers, and S.P. Creighton zyxwv Department of Medical Genetics, University of British Columbia (D.M.G., J.M.F., S.P.C.); Division of Pediatric Oncology-Hematology, British Columbia Children's Hospital, Vancouver, British Columbia (P.C.J.R.I. Acquired monosomy 7 is a frequent finding in myelodysplastic syndromes, including acute myelogenous leukemia. A subset of these pa- tients has been described with an apparently distinct condition: myelodysplasia and leuke- mia syndrome with monosomy 7 (MLSM7). We report 2 brothers, 3 and 5 years of age, with MLSM7 and review other reports of familial occurrence. Genetic factors appear to be im- portant in the cause of MLSM7, but the re- ported families do not fit neatly into any monogenic pattern. Recognition of the fre- quently familial nature of this condition re- quires hematological evaluation and genetic counseling for the families of patients with MLSM7. KEY WORDS: monosomy 7, myelodysplasia, leukemia, familial. INTRODUCTION The myelodysplastic syndromes comprise a variety of disorders involving abnormalities of hematopoiesis with frequent progression to acute myelogenous leukemia. Recently, attention has been focused on a subset of these disorders with bone marrow monosomy 7. Several famil- ial cases have been reported [Kamiyama et al., 1973; Larsen and Schimke, 1976; Li et al., 1978, 1981; Chi- tambar et al., 1983; Carroll et al., 1985; Paul et al., 1987; Brandwein et al., 19891; the causal significance of the loss of chromosome 7 has been the subject of some spec- ulation [Carroll et al., 1985; Shannon et al., 19891. We review the literature and discuss myelodysplasia and leukemia syndrome with monosomy 7 (MLSM7) from a genetic perspective. Received for publication June 2, 1989; revision received August 24, 1989. Address reprint requests to Dr. D. Gilchrist, Department of Medical Genetics, University Hospital, Shaughnessy Site, Van- couver, B.C., Canada V6H 3N1. BONE MARROW MONOSOMY 7 Acquired loss of chromosome 7 or the long arm of chromosome 7 (7q - ) has been described in de novo and secondary myelodysplastic syndromes of adults and children [Second International Workshop, 1980; Rowley et al., 1981; Fourth International Workshop, 1984; Mus- ilova and Michalova, 19881. Monosomy 7 is the most frequent chromosomal abnormality found in pre- leukemia [Second International Workshop, 19801 and the second most frequent numerical abnormality in acute nonlymphocytic leukemia (ANLL) LRowley, 19801. Monosomy 7 has also been seen in de novo forms of refractory anemia and myelodysplasia [Li et al., 1978, 1981; Chitambar et al., 1983; Paul et al., 1987: Brand- wein et al., 19891, myelofibrosis [Hagemeijer et al., 19801, myeloproliferative disorder [Linch et al., 1982; Pasquali et al., 19821,preleukemia [Boetius et al., 1977; Nowell, 19821, and frank leukemia [Petit et al., 1973; Borgstrom et al., 19801, hut only rarely in de novo ALL [Chan et al., 19851.Monosomy 7 is frequently associated with secondary myelodysplastic syndromes and leuke- mias [Secker-Walker and Sandler, 1978; Rowley et al., 19811. In this heterogeneous group of conditions, monosomy 7 may be the sole acquired cytogenetic abnormality; it may also be associated with other clonal chromosomal abnormalities. Trisomy 8 and monosomy 5 can be found concomitantly in patients with myelodysplastic disor- ders [Second International Workshop, 1980; Fourth In- ternational Workshop, 1984; Musilova and Michalova, 19881, and other complex chromosome losses, additions, or rearrangements have been described. Monosomy 7 may not be detectable at the initial diagnosis of hema- tological abnormality [Chitambar et al., 1983; Paul et al., 19871 but may be observed with worsening of the disorder. It may also occur as a transient abnormality during the evolution of disease [Rowley et al., 19811. When monosomy 7 is present in any form of my- elodysplasia, the prognosis is uniformly poor, with most patients succumbing to complications of pancytopenia or leukemia within months to a few years [Borgstrom et al., 1980; Yunis et al., 1986; Yunis and Brunning, 19861. The only effective treatment currently available is bone marrow transplantation [Sieff et al., 19811. zy 0 1990 Wiley-Liss, Inc.