Mosaic variegated aneuploidy with multiple congenital abnormalities: Homozygosity for total premature chromatid separation trait

Abstract

Separation of chromatids of all mitotic chromosomes, here called total premature chromatid separation (total PCS), was observed in 67 to 87.5% of repeated cultures of peripheral blood lymphocytes from two unrelated infants. Also noted was a variety of mosaic aneuploidies, especially trisomies, double trisomies, and monosomies, to be called mosaic variegated aneuploidy. The infants both showed severe pre- and postnatal growth retardation, profound developmental retardation, uncontrollable seizures, severe microcephaly, hypoplasia of the brain, Dandy-Walker anomaly, abnormal facial appearance, and bilateral cataract. Patient 1, a girl, in addition had a cleft palate, multiple renal cysts, and Wilms tumor of the left kidney. Whereas patient 2, a boy, had ambiguous external genitalia. They both died within 2 years of age. In the two families of the infants, their parents and three other members showed 2.5 to 47% lymphocytes with total PCS but without mosaic variegated aneuploidy or phenotypic abnormalities. Another 10 relatives studied showed 0 to 1% cells with total PCS and so were judged negative for the total PCS trait. It was deduced that the total PCS trait in the two families was transmitted in an autosomal-dominant fashion, and the two affected infants were homozygous for the trait.

Syndrome of microcephaly, Dandy-Walker malformation, and Wilms tumor caused by mosaic variegated aneuploidy with premature centromere division (PCD): report of a new case and review of the literature

“…Our patient had dilatation of the fourth ventricle and hypoplasia of the cerebellar vermis, features which were consistent with Dandy-Walker malformation. This anomaly was also seen in the patients described by Kajii et al (1998). Although the etiological relationship between Dandy-Walker malformation and multiple aneuploidies was not clear, these structural brain anomalies are most likely features of this syndrome, together with the findings reported by Kajii et al (1998).…”

“…Both showed PCD, in 42.5% of 200 cells from the mother and in 5% of 200 cells from the father. The control rate of PCD is less than 2% of cells (Kajii et al 1998). No aneuploid cells in 20 metaphases were detected in either parent.…”

“…Since the multiple congenital anomalies/mental retardation syndrome associated with this cytogenetic phenomenon was first reported by Scheres et al (1986), to date, only several patients have been reported (Tolmie et al 1988;Papi et al 1989;Miller et al 1990;Warburton et al 1991;Limwongse et al 1997;Nash et al 1997;Flejter et al 1998;Kajii et al 1998). Clinical features in the reported patients were variable, but growth retardation and microcephaly were frequently described.…”

“…In some patients, premature centromere division (PCD) was associated with numerical aneuploidies (Scheres et al 1986;Miller et al 1990;Warburton et al 1991;Limwonge et al 1997;Kajii et al 1998). PCD is a cytogenetic phenomenon characterized by parallel separated rod-like sister chromatids in metaphase.…”

Aneuploidy and Cancer: From Correlation to Causation

“…According to the chromosomal theory these mutations are genetic equivalents of carcinogens that induce aneuploidy at high rates. This view is supported by the presence of aneuploidy in such patients prior to carcinogenesis, as for example in mosaic variegated aneuploidy patients [183,184], Bloom patients [182] and xeroderma patients [185], and by the presence of aneuploidy in the cancers of patients with retinoblastoma [186][187][188][189], mosaic variegated aneuploidy [183,184], xeroderma [185,190] and Bloom patients [182].…”