Prenatal Diagnosis and Imaging of Genetic Syndromes Judy A. Estroff C ONGENITAL ANOMALIES, both major and minor, are present in approximately 10% of newborn infants and account for nearly a quarter of perinatal deaths. Many anomalies are detected prenatally during the course of a preg- nancy that the patient and her caregivers hope will be “uneventful.” Identification of an anomaly be- fore birth has both advantages and disadvantages. Advantages include the opportunity to alter preg- nancy management or to allow the parents to choose not to continue the pregnancy; to educate and prepare the parents for the birth of an anoma- lous child; the choice to intervene in utero, during delivery, or immediately after birth; to allow the obstetrician and newborn medicine specialist to coordinate delivery and resuscitation plans; and to allow the parents to meet the pediatric specialists who will care for the infant after birth. Disadvan- tages include increased parental anxiety, costs of increased pregnancy surveillance, and the impact of diagnostic uncertainty on the patient’s imagers and caregivers. As the field of prenatal diagnosis continues to evolve and pregnant women opt to use the battery of tests available to screen for anoma- lies, more true abnormalities and variants of nor- mal will be detected. GENERAL PRINCIPLES OF FETAL IMAGING The following are general principles of fetal imaging: 1. Most fetuses look normal, especially in the first (13 weeks) and second (14-25 weeks) trimesters. Biologic variability accounts for many differences in the size of a fetus, or fetal body part, in the third trimester (26-40 weeks). 2. “Normal” = the same, nearly identical to other fetuses of the same gestational age. 3. When a fetus looks different, there may be a problem. 4. Structures that are too large, too small, or absent suggest an anomaly. 5. Some anomalies are life threatening or dev- astating, such as hypoplastic left heart or holoprosencephaly. Many are not, such as an isolated absent kidney or cleft lip. 6. Even though a problem is not devastating, it may require follow-up or treatment in utero or after birth. 7. An isolated anomaly usually has a better outcome. 8. Multiple anomalies increase the risk of a chromosomal abnormality or syndrome. NUMERICAL CHROMOSOME ABNORMALITIES In a normal human, there are 22 pairs, a “dip- loid” number, of autosomes, which are chromo- somes other than sex chromosomes. Normal fe- male humans have a 46 XX karyotype because they have 44 paired autosomal chromosomes + 2 X sex chromosomes. Normal male humans have a 46 XY karyotype because they have 44 paired autosomes + 1 X and 1 Y sex chromosome. Aneuploidy is any deviation from the human diploid number of 46 chromosomes. Most aneu- ploidy is caused by nondisjunction during cell division, such that one cell receives an unequal number of the pair of homologous chromosomes. For example, in Turner syndrome, or monosomy X, the embryo’s cells are “hypodiploid,” 45X. In Down syndrome, the embryo’s cells are “hyperdip- loid,” expressed as 47 XX or 47 XY. The spectrum of chromosomal aberrations is wide ranging. Com- mon genetic syndromes include trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), Turner syn- drome, and triploidy. An in-depth discussion of all genetic syndromes is beyond the scope of this article. The reader is referred to the many excellent available texts that cover genetic syndromes in detail and depth. 1-8 Several of the most common chromosomal anom- alies, T21, T18, T13, Turner syndrome, and trip- loidy, have been selected for discussion here be- cause of their prevalence and as a vehicle to discuss specific nomenclature that may aid the clinician in understanding and categorizing an anomaly. 6 From the Department of Radiology, Children’s Hospital, Boston, MA. Address reprint requests to Judy Estroff, MD, Department of Radiology, Children’s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115. © 2004 Elsevier Inc. All rights reserved. 0037-198X/04/3902-0012$30.00/0 doi:10.1053/j.ro.2004.02.001 323 Seminars in Roentgenology, Vol 39, No 2 (April), 2004: pp 323-335