arm of another chromosome, often chromosome 14 [46,XX,t(14;21)] or itself [called an isochromosome, 45,XX,t(21;21)(q10;q10)] as seen in the translocation karyotype figure. Translocation Down syndrome can be de novo; that is, not inherited but occurring at the time of an individual's conception, or may be inherited from a parent with a balanced translocation. The balanced translocation figure shows a 14/21 translocation between the long arms of chromosomes 14 and 21, where the other chromosomes are not shown. The individual has two copies of everything on chromosome 14, and two copies of all of the material on the long arm of chromosome 21 (21q). The derivative chromosome 21, which contains only heterochromatin, is lost; thus, the individual only has one copy of the material on the short arm of chromosome 21 (21p), but this appears to have no discernible effect. Individuals with this chromosomal arrangement have 45 chromosomes and are phenotypically normal. During meiosis, the chromosomal arrangement interferes with normal separation of chromosomes. Possible gametic arrangements are (see translocation karyotype figure): 1. translocated 14/21 and normal 14; 2. normal 14 and normal 21; 3. translocated 14/21 and normal 21; 4. normal 21 only; 5. normal 14 only; 6. translocated 14/21 only. When combined with a normal gamete from the other parent, the first, fourth and fifth are lethal, leading to spontaneous abortion. The second, combined with a normal gamete from the other parent, gives rise to a typical child. The third leads to a translocation Down syndrome child. The last becomes a translocation carrier, like the parent. Translocation Down syndrome is often referred to as familial Down syndrome. It is the cause of about 4.5% of the observed Down syndromes. It does not show the maternal age effect, and is just as likely to have come from fathers as mothers. Mosaicism Mosaic Down syndrome is when some of the cells in the body are normal and some cells have trisomy 21, an arrangement called a mosaic (46,XX/47,XX,+21). This can occur in one of two ways: A nondisjunction event during an early cell division leads to a fraction of the cells with trisomy 21; An anaphase lag of a chromosome 21 in a Down syndrome embryo leads to a fraction of euploid cells (2n cells), phenomenon described as "aneuploidy rescue". There is considerable variability in the fraction of cells with trisomy 21, both as a whole and tissue-by-tissue. This is the cause of