Mosaic variegated aneuploidy with microcephaly: a new human mitotic mutant?

We report the case of a 17 year old girl with severe microcephaly and mental retardation, in whom karyotype analysis of PHA-stimulated lymphocytes, cultured skin fibroblasts, direct and cultured bone marrow and EBV-transformed lymphoblasts all showed at least 10% of cells with trisomy, which could be for many different chromosomes. All trisomies except 5, 10, 13, 14 and 17 were observed. Tissue-specific differences in the predominant trisomy occurred. The existence of this mosaic trisomy in four different tissues and in repeated cultures over a three year period suggests that it is due to a genetic abnormality resulting in mitotic instability. This case is compared with six previously reported human cases with a similar phenomenon, including two pairs of siblings. It is unclear whether all cases represent the same condition, since clinical and cytogenetic differences exist among them. The term "mosaic variegated aneuploidy with microcephaly" is suggested as a descriptive term for this syndrome.