It has been estimated that around 50% of all human conceptions are lost either before implantation at 5 to 6 days postconception or shortly afterwards (i.e., before the woman realizes she is pregnant). Among recognized pregnancies, at least 15% end in spontaneous miscarriage before 12 weeks' gestation. Even when material from the abortus can be obtained, it is often very difficult to establish why a pregnancy loss has occurred. However, careful study of large numbers of spontaneously aborted embryos has shown that gross structural abnormalities are present in 80% to 85%. These abnormalities vary from complete absence of an embryo in the developing pregnancy sac-a blighted ovum-to a very distorted body shape, or a specific abnormality in a single body system.
The development of a reliable technique for chromosome analysis in 1956 soon led to the discovery that several previously described conditions were due to an abnormality in chromosome number. Within 3 years, the causes of Down syndrome (47,XX/XY, +21), Klinefelter syndrome (47,XXY), and Turner syndrome (45,X) had been established. Shortly after, other autosomal trisomy syndromes were recognized, and over the ensuing years many other multiple malformation syndromes were described in which there was loss or gain of chromosome material. To date, at least 20,000 chromosomal abnormalities have been registered on laboratory databases. On an individual basis, most of these are very rare, but together they make a major contribution to human morbidity and mortality. Chromosome abnormalities account for a large proportion of spontaneous pregnancy loss and childhood disability, and also contribute to malignancy throughout life as a consequence of acquired translocations and other aberrations.
To date, more than 10,000 single-gene traits and disorders have been identified. Most of these are individually rare, but together they affect between 1% and 2% of the general population at any one time. The management of these disorders in affected individuals and in their extended families presents the major workload challenge in clinical genetics.