In Chapter 20 (Fetal Syndromes), several syndromes, the majority of which could be traced to genetic anomalies, were reviewed.* In this chapter, syndromes and associated findings that can be traced to chromosomal anomalies are reviewed. Many standard textbooks1,2,3,4,5,6, and 7 and other sources8,9 have been used to write this chapter; hence, specific points have not been cited; these are considered basic sources and should be part of every library.
Figure 21-1 shows the increase in frequency of aneuploidy with advancing maternal age.10,11 After 35 years of age, the risk increases steeply, not only for trisomy 21 but also for other aneuploidies in general. Some chromosomal anomalies are increased with the maternal age, and these include trisomies 13, 18, and 21, but not all chromosomal anomalies are increased with maternal age; in particular, triploidy and most of the sex chromosomal aneuploidies do not increase with maternal age.
Frequency of aneuploidy per 10,000 deliveries according to maternal age at delivery. (Data from Hecht CA, Hook EB: The imprecision in rates of Down syndrome by 1-year maternal age intervals: a critical analysis of rates used in biochemical screening, Prenat Diagn. 1994;14: 729-738. Bray I, Wright DE, Davies C, Hook EB: Joint estimation of Down syndrome risk and ascertainment rates: a meta-analysis of nine published data sets, Prenat Diagn. 1998;18:9-20.)
Fetuses that have structural anomalies often also have chromosomal anomalies (Figure 21-2). Wladimiroff et al.12 and Palmer et al.13 demonstrated that between 10% and 30% of fetuses that have structural anomalies also have chromosomal anomalies. In their studies, approximately half of the fetuses had a trisomy, one-fourth had a monosomy, approximately 10% to 15% had a mosaic, and the remainder had a few triploidies and miscellaneous aneuploidies.
Frequency of aneuploidies versus the number of anomalies. (Adapted Data from Nicolaides KH, Brizot ML, Snijders RJ: Fetal nuchal translucency: ultrasound screening for fetal trisomy in the first trimester of pregnancy. Br J Obstet Gynaecol. 1994;101: 782-786.)
In addition, Nicolaides et al.14 showed that babies who have more than one anomaly are more likely to have chromosomal anomalies, and the graph from their study clearly demonstrates this association.
Plachot et al.15 conducted a very interesting study in which eggs fertilized in vitro were used to assess the frequency of chromosomal anomalies in the fertilized eggs. In those experiments, 38% of the fertilized eggs demonstrated an aneuploidy (26% due to aneuploid oocytes, 8% to aneuploid sperm, 2% to polyploidy, and 6% to parthenogenesis). However, in practice, 38% of embryos do not demonstrate aneuploidies ...