Journal of Obstetrics and Gynaecology
ISSN: 0144-3615 (Print) 1364-6893 (Online) Journal homepage: http://www.tandfonline.com/loi/ijog20
Prenatal diagnosis of double trisomy 48, XXX, +18; case report Fedi Ercan, Pelin Taşdemir, Aybike Tazegül Pekin, Berkan Sayal, Hüseyin Görkemli & Ali Acar To cite this article: Fedi Ercan, Pelin Taşdemir, Aybike Tazegül Pekin, Berkan Sayal, Hüseyin Görkemli & Ali Acar (2018): Prenatal diagnosis of double trisomy 48, XXX, +18; case report, Journal of Obstetrics and Gynaecology, DOI: 10.1080/01443615.2017.1398220 To link to this article: https://doi.org/10.1080/01443615.2017.1398220
Published online: 13 Feb 2018.
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JOURNAL OF OBSTETRICS AND GYNAECOLOGY, 2018 https://doi.org/10.1080/01443615.2017.1398220
CASE REPORT
Prenatal diagnosis of double trisomy 48, XXX, 118; case report €rkemlia and Ali Acara €l Pekina, Berkan Sayala, Hu €seyin Go Fedi Ercana, Pelin Tas¸demirb, Aybike Tazegu a Meram Faculty of Medicine, Department of Obstetrics and Gynecology, Necmettin Erbakan University, Konya, Turkey; bMeram Faculty of Medicine, Department of Medical Genetics, Necmettin Erbakan University, Konya, Turkey
Introduction The synchronous occurrence of double trisomy (DT) involving chromosomes 18 and X is rare. Rarely, affected cases have been reported in infancy. However, DT is a relatively common event in pregnancies ending in early miscarriage (Jiang et al. 2015). Abnormalities of the chromosomes, usually caused by parental non-disjunction during gametogenesis, may affect the autosomal and sex chromosomes (Chen et al. 2000). DT in one individual is seen in 3% of foetuses with cytogenetic abnormalities (Jiang et al. 2015). The most common DT involving one of the sex chromosomes is a 48, XXY, þG male with Klinefelter’s and Down’s syndromes (Shen et al. 2012). To our knowledge, only 17 cases of 48, XXX, þ18 have been described. In this report, we present a case of DT 48, XXX, þ18 diagnosed in the third trimester of pregnancy, as the result of multiple foetal anomalies and cell-free DNA analysis.
Case report A 35-year-old gravida 2, para 1 woman was referred for genetic counselling in the third trimester because of abnormal ultrasonographic findings. At 16 weeks of gestation, she had a maternal serum screening test, which showed a Down syndrome risk of 1:843 calculated from a maternal serum alpha-fetoprotein level of 1.09 multiples of the median. The pregnancy was uncomplicated until 24 weeks of gestation when intrauterine growth retardation and polyhydramnios were noted. Sonographic examination at 29 weeks of gestation showed a growth-retarded foetus with a biparietal diameter of 69 mm (28 weeks), an femur length of 55 mm (29 weeks), an abdominal circumference of 206 mm (25 weeks), an amniotic fluid index of 295 mm, a ventricular septal defect, a hyperechoic focus in the heart, clenched hands, rocker-bottom feet, extra-axial polydactyly of the hands, a strawberryshaped head and choroid plexus cysts. At the following screening, a non-invasive prenatal testing (NIPT) was performed at 29 þ 4 weeks of gestation, by collecting maternal peripheral blood for a cell-free foetal DNA (cffDNA) extraction, library construction and sequencing through the Illumina HiSeq2000 platform (Jiang et al. 2012). The NIPT demonstrated risks of foetal trisomies 18 and X. Genetic cordocentesis was performed. Chromosome analysis after a CONTACT Fedi Ercan 42080, Turkey
[email protected]
karyotype of 48, XXX, þ18 [20] (Figure 1(A)). To eliminate the mosaicism, an interphase fluorescence of in situ hybridisation (FISH) assay was applied to the cordocentesis material by using prenatal probes (AquariusV Prenatal Probes, Cytocell, UK) (Figure 1(B)). At 34 þ 1 weeks, the foetus was delivered by caesarean, due to preterm premature rupture of membranes; the woman had a previous caesarean delivery. Birth weight was 1550 g (
Discussion DT 48, XXX, þ18 is a rare chromosome abnormality which was first described by Uchida and Bowman (1961). Prenatal diagnosis of the simultaneous occurrence of DT involving chromosomes 18 and X is extremely rare. We reviewed the available literature. Only 17 cases with 48, XXX, þ18 have been reported and only four cases with 48, XXX, þ18 have been reported at intrauterine (Chen et al. 2000; van Huizen et al. 2004; Dezerega et al. 2005). With the case we report here, we aim to contribute to the characterisation of the sonographic and clinical features of this condition in third-trimester pregnancies. In the present case, the infant had typical trisomy 18 features. In contrast, trisomy X in isolation has not been reported in association with increased structural defects because this condition lacks specific phenotypic manifestations in the foetus (Gonen et al. 1995). Therefore, the primary sonographic features of DT 48, XXX, þ18 depend on the trisomy 18 complement. In the present case, it appeared that the extra X chromosome had not contributed to any phenotypic abnormalities in the infant. This is consistent with the findings of other studies that triple-X females are phenotypically normal. NIPT using cff-DNA in the maternal blood is a relatively new screening modality for the common trisomies of chromosomes 21, 18, and 13, and sex chromosome aneuploidies. Some professional societies and clinicians have recommended that NIPT be a screening test rather than a diagnostic test
Meram Faculty of Medicine, Department of Obstetrics and Gynecology, Necmettin Erbakan University, Konya
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Figure 1. Genetic examination of the foetus. (A) Karyotype of the proband (48, XXX, þ18). (B) Fluorescence in situ hybridisation (FISH) assay was used for the detection of double trisomy. Hybridisation signals on an inverted DAPI counterstain metaphase spread show three signals indicative of trisomy 18 and three signals indicative of trisomy X (arrows).
Figure 2. Findings at birth. (A) Extra-axial polydactyly of the hands and clenched hands. (B) Rocker-bottom feet.
because NIPT has a high failure rate and may increase the false positive rates, decrease the positive predictive value and increase the procedure-related pregnancy loss. As the source of cff-DNA is the placenta, confined placental mosaicism may explain a proportion of discordant NIPT results
(McCullough et al. 2014). Furthermore, discordancy between the cff-DNA results and foetal karyotype can be due to true foetal mosaicism, the presence of a maternal karyotype abnormality, insufficient counting due to low foetal fraction, or a vanishing twin (Cuckle et al. 2015). In this case,
JOURNAL OF OBSTETRICS AND GYNAECOLOGY
cordocentesis was planned to determine the karyotype because an NIPT test was performed at 29 þ 4 weeks of gestation and demonstrated risks of foetal trisomies 18 and X.
Disclosure statement The authors report no declarations of interest.
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Gonen R, Dar H, Degani S. 1995. The karyotype of fetuses with anomalies detected by second trimester ultrasonography. European Journal of Obstetrics, Gynecology and Reproductive Biology 58:153–155. Jiang F, Ren J, Chen F, Zhou Y, Xie J, Dan S, et al. 2012. Noninvasive Fetal Trisomy (NIFTY) test: an advanced noninvasive prenatal diagnosis methodology for fetal autosomal and sex chromosomal aneuploidies. BMC Medical Genomics 5:57. Jiang ZY, Wu XH, Zou CC. 2015. Double trisomy 48,XXX,þ18 with multiple dysmorphic features. World Journal of Pediatrics: WJP 11:83–88. McCullough RM, Almasri EA, Guan X, Geis JA, Hicks SC, Mazloom AR, et al. 2014. Non-invasive prenatal chromosomal aneuploidy testingclinical experience: 100,000 clinical samples. PLoS One 9:e109173. Shen Z, Zou CC, Shang SQ, Jiang KW. 2012. Down-Klinefelter syndrome (48,XXY,þ21) in a child with congenital heart disease: case report and literature review. Internal Medicine 51:1371–1374. Uchida IA, Bowman JM. 1961. XXX 18-trisomy. The Lancet 278:1904. van Huizen ME, Knegt AC, Bijlsma EK, et al. 2004. Double trisomy 48,XXX,þ18 in association with increased nuchal translucency; two cases. Prenatal Diagnosis 24:1020–1021.
