Report of two new cases of Pallister-Killian syndrome confirmed by FISH: tissue-specific mosaicism and loss of i(12p) by in vitro selection.

Tissue-specific mosaic distribution of an additional isochromosome 12p is the characteristic chromosomal aberration in Pallister-Killian syndrome. Often it is confined to fibroblasts, whereas lymphocytes show a normal karyotype. Two cases are reported in which the distribution of the additional i(12p) was analysed in various tissues. The isochromosomes were characterised by conventional banding technics and fluorescence in situ hybridization (FISH). In the first case, diagnosed prenatally, 4 different tissues were analysed. A direct preparation of chorionic villi (21 gestational weeks) showed an extra marker chromosome in 19% and two additional copies in 3% of the examined cells. In two cultures of amniocytes (17 and 21 weeks), the i(12p) was observed in 23% and 12%, respectively. It was absent in cultured lymphocytes of fetal blood (21 weeks). The fibroblast long-term culture of umbilical cord showed the i(12p) in 100% of metaphases. In the second case of a term infant the i(12p) was diagnosed in cultured lymphocytes (4%) and fibroblasts (93%). Secondary loss of the isochromosome was evaluated by in vitro selection in case 2 analysing metaphases and interphases of fibroblasts in the 1st, 4th and 5th subculture using FISH. The proportion of cells with i(12p) decreased from 93% to 40% and to 28%, respectively. DNA analysis in case 1 showed a maternal meiotic origin of the i(12p). The prenatally detected clinical findings in both cases showed characteristic abnormalities of the Pallister-Killian syndrome.