Other Autosomal Aneuploidies



Key Points

  • Trisomies 8,9,14,16, and 20, if present in mosaic form, are compatible with postnatal survival.

  • Mosaic trisomies are generally associated with nondisjunction due to advanced maternal age.

  • Trisomy 16 occurs in at least 1.5% of all clinically recognized pregnancies and 31% of all spontaneous losses due to chromosome abnormalities.

  • Trisomy 20 accounts for 2% oftrisomic miscarriages and is a common cause oftrue mosaicism in amniotic fluid cultures.

  • For mosaic trisomies 8,9, and 14, a detailed sonographic survey of fetal anatomy and consultation with a medical geneticist are indicated.

  • Women carrying fetuses with mosaic trisomy 16 are at riskfor developing pre-eclampsia.

  • Phenotype does not correlate with percent of mosaic cells except for trisomy 20. The presence of more than 60% of cells with trisomy 20 is associated with a poor prognosis.

  • All continuing pregnancies should have involvement of the medical genetics team.

  • Survivors with trisomy 16 have excellent postnatal catch-up growth and the majority have a good developmental outcome. Mosaic trisomies 8,9, and 14 have variable outcomes. Mosaic trisomy 20 has a normal outcome if thereare less than 60% abnormal cells.



In this chapter, information will be discussed regarding trisomies 8, 9, 14, 16, and 20. These are the trisomies that, if present in a mosaic form, are compatible with fetal survival at least until the end of the first trimester. They present with sonographic abnormalities or abnormalities of maternal serum screening analytes. All of these conditions are detected by cytogenetic analysis. Mosaic trisomies account for around 5% of the trisomies detected in human spontaneous abortions. In general, they are associated with advanced maternal age (James and Jacobs, 1996). For most of the trisomies, the general mechanism is nondisjunction in maternal meiosis I. This is then followed by a second mitotic error in chromosome division. The second division corrects the trisomy, but about a third of the time results in leaving behind two maternal copies of the particular chromosome. This is known as uniparental disomy (UPD). UPD can then cause an abnormal phenotype through homozygosity for recessive genes or if there are areas of imprinted genes on that particular chromosome (Reish et al., 1998). In contrast, current evidence seems to indicate that trisomy 8 has a different underlying mechanism. It appears to be due to postzygotic nondisjunction with a gain of a chromosome in some tissues.

Trisomies 8, 9, 14, 16 and 20 are generally lethal when present as a full trisomy. In this chapter only the mosaic trisomies will be discussed, as those are what is encountered clinically. For most of the mosaic trisomies, there is no relationship between the percent mosaicism and the clinical outcome, with the exception of trisomy 20.

Interestingly, all of the mosaic trisomies may present with postnatal skin pigmentation defects, such as hypomelanosis of Ito. The precise connection between mosaicism and the skin pigmentation defects is unknown. Also, a number of the mosaic trisomies can demonstrate subtle body asymmetries.



It is difficult to get accurate livebirth incidences for the mosaic trisomies. Most of the data that have been reported are from the prenatal diagnosis or the pathology literature. For example, full trisomy 16 is the most common trisomy that is found in spontaneous abortions. Trisomy 16 occurs in at least 1.5% of all clinically recognized pregnancies (Wolstenholme, 1995). This condition comprises 31% of all autosomal trisomies in products of conception. Similarly, trisomy 20 is one of the most common forms of autosomal mosaicism diagnosed at amniocentesis (Hsu et al., 1987). Mosaic trisomy 20 accounts for 2% of all trisomic miscarriages (Hsu et al., 1987; Robinson et al., 2005). Mosaicism for trisomy 8 has been detected in approximately 1 in 3870 amniocenteses (van Haelst et al., 2001). Trisomies 9 and 14 account for 2.7% and 3.7%, respectively, of chromosomally abnormal miscarriages (Fujimoto, 1992; Chitayat et al., 1995).



Trisomy 8

The sonographic findings for trisomy 8 include nuchal fold thickening, hemivertebrae, ventriculomegaly (Southgate et al., 1998), reversed end-diastolic ductus venosus blood flow (Campbell et al., 2001), pyelectasis, hydronephrosis, ureteral reflux, and cardiac abnormalities (Miller et al., 2001).

Trisomy 9

Stipoljev et al. (2003) reviewed the sonographic findings in 12 nonmosaic and 13 mosaic fetuses with trisomy 9. The sonographic abnormalities seen in full trisomy 9 included intrauterine growth restriction, microcephaly, increased nuchal translucency measurement, cystic hygroma, micrognathia, hydrops, decrease in the long bone measurements for age, congenital heart defects, skeletal abnormalities, and Dandy–Walker malformation. Dandy–Walker malformation (see Chapter 11) is seen in 12% to 15% of fetuses with trisomy 9. For the mosaic fetuses, the characteristic abnormalities are Dandy–Walker malformation, intrauterine growth restriction, micrognathia, and hydronephrosis. Other abnormalities associated with trisomy 9 include hepatic calcifications, diaphragmatic hernia, and male genital abnormalities.

Trisomy 14

There have been no comprehensive reports of prenatal sonographic findings in trisomy 14. However, from the postnatal literature, what might be expected would be intrauterine growth restriction, micrognathia, congenital heart disease (especially tetralogy of Fallot), polyhydramnios, and micropenis.

Trisomy 16

Characteristic pathologic findings associated with trisomy 16 include intrauterine growth restriction, congenital heart disease (atrial septal defect, ventricular septal defect, and tetralogy of Fallot), single umbilical artery, and renal anomalies. Astner et al. (1998) reported on sonographically associated anomalies associated with confined placental mosaicism for trisomy 16. They noted the presence of a thickened and enlarged cystic placenta. The cysts that were present in the second trimester but disappeared in the third trimester had an unusual appearance in that they were multiple and round without a hyper-reflective border. They speculated that this might be a sonographic marker for trisomy 16.

Trisomy 20

For the majority of cases of mosaic trisomy 20, the sonographic findings have been normal. James et al. (2002) reported on 14 cases of trisomy 20 mosaicism. Of these, three had an increased nuchal translucency measurement on a first trimester scan. The remaining 11 cases had a detailed second trimester anatomy scan that was normal. What might be expected from the postnatal literature would also be the possibility of a heart or renal malformation.



The diagnosis of each of these conditions is based on highly accurate cytogenetic analysis.



For all of these conditions, full trisomy is generally lethal in utero. Whether or not the fetus survives depends on a number of factors. These include whether or not the trisomy is confined to the placenta, whether or not there is a rescue disomy, and whether or not UPD of the remaining disomic chromosomes exists. Because trisomies 16 and 20 are more common than trisomies 8, 9, and 14, relatively more information is available.

Trisomy 16

In cases of mosaic trisomy 16, placental mosaicism is always present. In spontaneous abortions with trisomy 16, the extra copy of 16 is always maternal in origin (Hsu et al., 1998). The mosaic trisomy 16 cases that derive from full trisomy and undergo disomic rescue have approximately a 30% to 40% chance of maternal UPD for chromosome 16. If UPD for 16 is present, there is an increased incidence of both intrauterine growth restriction and congenital anomalies (Yong et al., 2002). Most cases of trisomy 16 spontaneously abort between 8 and 15 weeks of gestation (Wolstenholme, 1995; Benn, 1998). Trisomy 16 detected at amniocentesis is more likely to be associated with anomalies as compared with trisomy 16 detected at CVS, which is more likely to be due to confined placental mosaicism. It has been shown by many investigators that adverse fetal outcomes are more common when the trisomy is detected in the amniotic fluid (Yong et al., 2003; Langlois et al., 2006; Neiswanger et al., 2006).

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Dec 27, 2018 | Posted by in OBSTETRICS | Comments Off on Other Autosomal Aneuploidies
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