Occurs in 1% to 2% of clinically recognized conceptions but only 1/10,000 livebirths. Not associated with advanced maternal age.
Most cases are 69, XXY (60%) or 69, XXX (37%); only 3% of cases are 69,XYY.
In the type I phenotype the fetus is relatively well grown with a large cystic placenta.
In the type II phenotype the fetus is markedly growth restricted with a disproportionately large head and a small, noncystic placenta.
One third of cases survive beyond 15 weeks and are associated with abnormal maternal serum screen results.
The longest postnatal survival for an affected infant was 10frac12 months.
Triploidy is defined as the presence of three complete sets of the normal haploid genome found in gametes. Triploidy occurs in one of three ways: (1) failure of division in meiosis I or II in the spermatocyte, resulting in an extra set of paternal chromosomes (diandry); (2) failure of division in meiosis I or II in the oocyte, resulting in an extra set of maternal chromosomes (digyny); or (3) double fertilization of a normal haploid ovum (dispermy). Using special chromosome-staining techniques, it has been shown that the extra set of chromosomes is paternal in origin in three quarters of cases (Jacobs et al., 1982). Most of the paternally derived cases are due to dispermy (Kajii and Niikawa, 1977). The distribution of karyotypes seen in triploid conceptuses is 69, XXY (60%), 69, XXX (37%), and 69, XYY (3%) (Jacobs et al., 1982). The infrequent occurrence of XYY suggests that either diandry must be uncommon or that XYY carries a disadvantage for survival.
Triploid fetuses can present with a broad spectrum of phenotypic features that can range from near normalcy to multisystem involvement. McFadden and Kalousek (1991) have described two distinct fetal and placental phenotypes that appear to correlate with the parent of origin in the extra set of chromosomes. In the type I phenotype, the fetus is relatively well grown and has a proportionate head size or microcephaly. The placenta is large, with cystic changes. At the microscopic level there is trophoblastic hyperplasia, scalloping of the villus surface, and focal hydropic change (Sergi et al., 2000). These cases are generally associated with diandry (Figure 132-1A). The type II phenotype predominates in the cases diagnosed after the first trimester; it consists of a markedly growth-restricted fetus with a disproportionately large head and a small, noncystic placenta (Figure 132-1B). In their series, McFadden and Kalousek were able to demonstrate that one case of type II triploidy originated from an error in maternal gametogenesis.
A. Relatively well-grown fetus with large cystic placenta seen in type I triploidy. B. Markedly growth-restricted fetus with a disproportionately large head and a small, noncystic placenta seen in type II triploidy. (Reprinted from McFadden DE, Kalousek DK. Two different phenotypes of fetuses with chromosomal triploidy: correlation with parental origin of the extra haploid set. Am J Med Genet. 1991;38:535-538. Copyright 1991 John Wiley & Sons. Reprinted, by permission, of John Wiley & Sons, Inc.)
Human triploidy is a relatively common condition, occurring in 1% to 2% of all clinically recognized conceptions (Jacobs et al., 1978). Triploidy accounts for approximately 20% of spontaneous abortions due to chromosomal abnormalities (Niebuhr, 1974; Wertelecki et al., 1976). After Turner syndrome (45, X), triploidy and trisomy 16 are the most common chromosomal abnormalities diagnosed in first trimester products of conception (Lindor et al., 1992). The early pregnancy wastage is high—for each triploid infant born alive, it is estimated that 1200 are miscarried (Doshi et al., 1983).
Although triploid conceptions are very common, the incidence is only 1 per 10,000 livebirths (Jacobs et al., 1982). There is no evidence for an increased risk due to advanced maternal age (Rochon and Vekemans, 1990). In experimental animals, triploidy has been induced by colchicine administration, hypoxia, and heat shock (Niebuhr, 1974). There is a questionable association between triploidy and delayed fertilization, due to prolonged menstrual cycles or discontinuation from oral contraceptives (Niebuhr, 1974). Uchida and Freeman (1985) have described an association between pre-conceptual diagnostic abdominal X-ray exposure and subsequent triploid conceptuses.
No single anomaly on sonographic examination is pathognomonic of triploidy (Pircon et al., 1989a). The diagnosis of triploidy should be suspected in any pregnancy with cystic placental changes and fetal anomalies. Similarly, severe intrauterine growth restriction and a markedly increased head: body size ratio should elicit consideration of triploidy (Figure 132-2).
Intrauterine growth restriction in triploidy has been reported as early as the first trimester (Benacerraf, 1988), but the classic presentation is in the second trimester. Crane et al. (1985) have described growth curves for triploid fetuses studied on several occasions during gestation. The characteristic finding is an abnormally increased head:abdominal circumference ratio that gives the appearance of relative macrocephaly. Oligohydramnios has been reported in as many as 60% of cases (Mittal et al., 1998). Hydrocephalus is common and can be seen in the first trimester (Crane et al., 1985; Benacerraf, 1988). Facial anomalies include micrognathia, microphthalmia (Wertelecki et al., 1976), a bulbous nose, and a small mouth (Bendon et al., 1988). A relatively specific finding is syndactyly of the third and fourth digits (Figure 132-3) (Bendon et al., 1988). Approximately 25% of triploid fetuses have a neural tube defect (Gosden et al., 1976) and 10% to 18% have associated omphalocele or gastroschisis (Blackburn et al., 1982). Male triploid fetuses may have genital abnormalities. Ambiguous genitalia may also be due to the presence of a mosaic karyotype, with two cell lines that contain different sex chromosomes. Both polyhydramnios and oligohydramnios have been described. Other fetal findings that may be apparent sonographically include cardiac anomalies (ventricular septal defect and atrial septal defect), pulmonary hypoplasia, and renal cystic changes. It should also be noted that the absence of anomalies does not preclude a diagnosis of triploidy.
Placental abnormalities are typical of type I (diandric) triploidy (Mittal et al., 1998). Characteristic findings include placental enlargement, hydropic changes (Wertelecki et al., 1976), a generalized hyperechoic appearance, and the presence of multiple small or a single large cyst (see Figure 132-1) (Rubenstein et al., 1986). Abnormal placental Doppler studies are also common (Jauniaux, 1999).
In cases in which triploidy is suspected, sonographic examination of the maternal ovaries may reveal the presence of associated theca lutein cysts (Meizner et al., 1991).