Genetic aspects of miscarriage

Fetal chromosome abnormalities account for about 50% of first-trimester pre gnancy losses. Most of these abnormalities are numerical abnormalities (86% ) and a low percentage is caused by structural abnormalities (6%) or other genetic mechanisms, including chromosome mosaicism (8%). The recurrence ris k of numerical abnormalities is low, so karyotyping of fetal material in ca se of a miscarriage does not seem worthwhile in daily practice. Half of the structural abnormalities may be inherited from a parent carryin g a balanced chromosome translocation or inversion. Parental carriership is found in 4-6% of the couples with recurrent miscarriage. In case of parent al carriership of a balanced structural chromosome abnormality, a next preg nancy may result in a child with an unbalanced structural chromosome abnorm ality. This child can have multiple congenital malformations and/or a menta l handicap. Prenatal diagnosis is therefore recommended. Conventional laboratory techniques, such as tissue culturing and karyotypin g, or (semi-)direct chromosome technique of chorionic villi, and the recent ly developed laboratory techniques such as fluorescence in situ hybridizati on (FISH) and comparative genomic hybridization (CGH), are described succes sively. Until now, not enough evidence has been available about the role of other g enetic mechanisms, such as single-gene abnormalities, uniparental disomy, g enomic imprinting, multifactorial disorders and skewed X chromosome, in the occurrence of miscarriages.