Maternal origin of 47,XXY and confined placental mosaicism 47,XXY/48,XXY,+13 in an infant conceived through IVF

Abstract

Klinefelter syndrome (47,XXY) has a prevalence of 0.1–0.2 % in the general population and is characterized by small firm testes, gynecomastia, hypogonadism, and an increased level of serum follicle-stimulating hormone (FSH) [23]. Klinefelter syndrome often results in infertility and has been observed in the infertile male population at an incidence of 3.1 % [23]. Unlike autosomal trisomies in which approximately 10 % of cases are of paternal origin, in about half of cases of Klinefelter syndrome, the extra chromosome is of paternal origin [23]. These errors only arise from nondisjunction in meiosis I when of paternal origin, and more commonly meiosis I rather than meiosis II when of maternal origin [23]. Some studies have shown an increased risk of Klinefelter syndrome with advanced maternal and paternal age [5,10,25]. This is thought to be due to greater rates of meiotic nondisjunction errors in aging gametes. Individuals of advanced age commonly utilize assisted reproductive technologies (ARTs). Infertile individuals have been shown to have more chromosome abnormalities in their gametes compared to fertile individuals [8,14,31]. Chromosome abnormalities in the sperm of men with abnormal semen parameters have been observed despite a normal karyotype, particularly for sex chromosomes [21,27,35,36]. Through the utilization of ARTs, a higher risk of producing a 47,XXY conception may exist. Aneuploid conceptions can also involve confined placental mosaicism (CPM), a term used to describe the presence of multiple cell lines in the placenta and not the fetus. Pregnancies with CPM have a 22 % higher rate of loss [18], a 9.3 % increased risk of growth restriction [29], and an overall 16–21 % risk of prenatal or perinatal complications [19]. The incidence of CPM is 2 % in first trimester chorionic villus sampling of viable pregnancies, making it the most frequent type of constitutional chromosomal mosaicism [24]. The most common abnormality in CPM is trisomy [18]. Aneuploid pregnancies have been associated with infertility, especially in women of advanced maternal age (AMA). The obstacle of AMA can be overcome with in vitro fertilization (IVF) treatment in some cases. Although IVF is associated with an increased risk of an abnormal embryo, it has not been observed to increase the overall risk for CPM when compared to natural conception [6,15]. We report a unique case of Klinefelter syndrome (47,XXY) detected in a newborn conceived through IVF. On analysis of the placenta, a portion was found to contain trisomy 13 as well (47,XXY/48,XXY,+13). Investigations into the origins of the extra chromosomes were completed to see if this may have been a case of double trisomy with subsequent trisomic rescue, or an error in gametogenesis followed by a somatic mutation within the embryo. In light of the first option, the possibility of uniparental disomy (UPD) 13 in the infant was also evaluated. To our knowledge, this is the first report of such a case.