Non-Invasive Prenatal Testing (NIPT)
Carlos Simón, Carmen Rubio in Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
The frequency of SCAs is around 1.88/10,000 births (38). Testing for SCAs was first incorporated as a screening option in 2012 for monosomy X (39). This was promptly followed by testing for other SCAs, including 47, XXX; 47, XXY; and 47, XYY; which are frequently mild or asymptomatic and do not meet the classical criteria for population-based screening. However, the NIPT performance for the X and Y chromosomes is not as accurate as it is for chromosome 21 (40). The most recent meta-analysis estimated the sensitivity for monosomy X detection at 95.8% with an FPR of 0.14%. For the other SCAs, the DR was estimated at 100% and FPR at 0.004% (14) (Table 26.1).
Sex Chromosome Anomalies
Merlin G. Butler, F. John Meaney in Genetics of Developmental Disabilities, 2019
Sex chromosome aneuploidy has been shown to be relatively common. Males may have XXY or XYY karyotypes. Females may have trisomy X (47,XXX) or monosomy X (45,X). Individuals with four and five sex chromosomes have also been described, as well as individuals with sex chromosome mosaicism (e.g., 45,X/46,XX; 46,XY/47,XXY) or structural rearrangements of the X and Y chromosomes. Such abnormalities may result in infertility or hypogonadism, and perhaps lower intelligence, but usually cause little morbidity or mortality. The one exception is the 45,X karyotype that results in a 99% fetal loss during gestation (3).
The Genetics of Spontaneous Abortions
Howard J.A. Carp in Recurrent Pregnancy Loss, 2020
Monosomy X accounts for 15%–20% of chromosomally abnormal miscarriages. Early monosomy X abortuses usually consist of only an umbilical cord stump. If a 45,X embryo survives until later in gestation, anomalies characteristic of Turner syndrome may be manifested [53]. These include cystic hygromas, generalized edema, and cardiac defects. Unlike most live-born 45,X infants, abortuses show ovarian germ cells. Approximately 80% of live-born monosomy X is the result of paternal sex chromosome loss [54].
Disproportion and dysmorphism in an adult Belgian population with Turner syndrome: risk factors for chronic diseases?
Published in Acta Clinica Belgica, 2020
An-Sofie Van De Kelft, Charlotte Lievens, Katya De Groote, Laurent Demulier, Julie De Backer, Guy T’Sjoen, Margarita Craen, Bert Callewaert, Jean De Schepper
Table 1 shows the clinical characteristics of the study population and their comparison between the different categories of dysmorphic severity. The age of the TS females ranged from 18 to 53 (mean 33.4) years and their BMI from 18.2 to 39.6 (mean 25.0) kg/m2. Monosomy X was present in 13 out of 44 women, mosaicism was present in 12/44 women and structural abnormalities of the X chromosome were present in the remaining 15 TS women. Monosomy X was found in all 3 patients with a high dysmorphism score, while only 1 of the 12 patients with a low score had a 45,X0 karyotype (data not shown). In total, 13 (29.5%) women had a standing height below 150 cm. 21 women (50%) had a BMI > 25kg/m2. SNHL and AHT were the most frequently recorded chronic disorders, affecting respectively 20 (45.5%) and 18 (40.9%) of the studied TS women. Hearing aids were used by 7 (15.9%) TS women, antihypertensive medication was taken by 16 (36.4 %) women.
Early Pregnancy Losses: Review of Nomenclature, Histopathology, and Possible Etiologies
Published in Fetal and Pediatric Pathology, 2018
M. Halit Pinar, Karen Gibbins, Mai He, Stefan Kostadinov, Robert Silver
Among chromosomal abnormalities in early pregnancy losses, 86%–91% are numerical chromosomal abnormalities, which can be subdivided into aneuploidy (trisomies and monosomies) and polyploidy. Increasing maternal age increases risk for aneuploidy and, indeed, increases the risk for miscarriage. Risk of early pregnancy loss ranges from 8.9% in women ages 21–25 years to 74.7% in women older than 45 years (45). Trisomies are the most frequently occurring numerical chromosomal abnormalities (52%–63%), followed by polyploidy (17%–21%) and monosomy X (11%–13%) (8,46). Most trisomies occur as a consequence of nondisjunction during maternal meiosis I. Trisomy 16 is the most common trisomy in pregnancy loss specimens, followed by trisomies of 22, 15, and 21 (9). Monosomy X is also common and usually occurs as a result of paternal sex chromosome loss. Autosomal monosomies are less common than monosomy X (2).
Early prenatal diagnosis of 49,XXXXY: two case reports
Published in Journal of Obstetrics and Gynaecology, 2019
Yue-Cheng Lu, Lv-Yin Huang, Yan-Dong Yang, Dong-Zhi Li
In this study, we first reported a prenatal case of 49,XXXXY that was detected by cfDNA testing. Interestingly, Stover et al. present a 49,XXXXY case in which cfDNA testing identified extra X chromosomes, but misreported as 47,XXX (Stover et al. 2017). Due to its extreme rarity, it is impossible to assess the test performance of cfDNA testing in this gonosomal disorder. However, there have been studies defining the performance of cfDNA for the assessment of foetal SCA risk. Reiss et al. (2017) reported the suspected cases of SCA by cfDNA testing in 18/2851 (0.63%) patients. The false positive rate for monosomy X was high (91%; 10/11), whereas two cases of 47,XXY and five cases of triple X were accurately predicted. Bevilacqua et al. (2017) reported that a total of 161 cases were screened as positive for SCA in 1957 patients. The positive predictive value (PPV) was 24.6% for 45,X, 22.7% for triple X, 63.3% for 47,XXY and 100% for 47,XYY. The authors concluded that SCAs involving the Y chromosome had a higher PPV than those involving the X chromosome. SCA was frequently suspected in cfDNA testing. Since cfDNA cannot discriminate the exact X copies in male foetuses with supernumerary X karyotypes, our first case supports an invasive genetic testing over cfDNA in the setting of an increased risk of 47,XXY.
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