Myeloproliferative Syndrome, Transient
Transient myeloproliferative syndrome is a leukemoid reaction that occurs in some newborn infants with Down syndrome and rarely in phenotypically normal infants (Seibel et al., 1984). In 9 Down syndrome patients with transient myeloproliferative syndrome, Niikawa et al. (1991) found that the mode of inheritance of centromeric chromosomal markers was compatible with duplication of one parental chromosome 21. Therefore, they proposed a hypothesis of 'disomic homozygosity' of a mutant gene on chromosome 21 as the causative mechanism (Abe et al., 1989). Niikawa et al. (1991) observed a Down syndrome patient who had an inversion of one chromosome 21; by studies with DNA polymorphic markers in 5 other patients, they obtained results suggesting that the putative gene (which they symbolized TMS) was located at 21q11.2.
Cytogenetic and molecular studies demonstrated that in Down syndrome associated with transient abnormal myelopoiesis, trisomy 21 had arisen much more frequently through mitotic (or meiosis II) nondisjunctions than through meiosis I errors (Shen et al., 1995). This supported the notion of 'disomic homozygosity' of a certain locus on chromosome 21 in 21-trisomic cells. In these patients there was no evidence of maternal age effect (Iselius et al., 1990). Like Niikawa et al. (1991), Shen et al. (1995) mapped the putative TAM gene to the pericentromeric region, 21q11.1-q11.2. In the 7-day-old male with Down syndrome and TAM reported by Niikawa et al. (1991), Ohta et al. (1996) isolated a cosmid clone corresponding to the inv(21) breakpoint, on the presumption that in this patient the putative TAM gene was disrupted by the break. The mother had the same inversion, and the father had a normal karyotype. The leukemoid reaction disappeared spontaneously several months after birth. Ohta et al. (1996) noted there was no evidence of imprinting on chromosome 21; thus, they speculated that disruption of a putative TAM gene may be the basis of the abnormality. The existence of a fusion gene is unlikely because almost no cases of TAM in Down syndrome had been reported with a rearranged chromosome 21 such as was observed in this critical case.