Topic > Paternal age: the notable confounding risk factor in chromosomal aneuploidies

IndexAbstractIntroductionObjectivesMATERIALS AND METHODSResultsDiscussionConclusionAbstractThe association between advanced maternal age and chromosomal aneuploidies has been widely discussed and debated over decades. The effect of paternal age was underestimated and left room for analysis and discussion. In a retrospective study, we observed the paternal age of three chromosomal aneuploidies from the Indian population. Data from patients with confirmed karyotype included paternal age. Paternal age was dichotomized into two groups (≤ 30 years) and (> 30 years). Linear regression analysis was applied to observe the correlation between paternal age and children born with aneuploidy. Interestingly, we could infer statistically significant paternal age as a confounding risk factor in chromosomal aneuploidy in both age groups for Down and Turner syndrome. These observations have facilitated the need for a strategic approach in the management of couples at risk of cytogenetic abnormalities. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay Introduction Gametogenesis represents an integral phenomenon in reproductive cycles. Meiotic errors tend to produce abnormal germ cells with missing or extra chromosomes, causing aneuploidy. A higher percentage of abnormal oocytes (21%) than spermatozoa (9%) was observed (Martin HR 2008); the difference may be due to checkpoints during spermatogenesis. Advanced maternal age, the major factor in oocyte aneuploidy (Griffin 1996), has been widely discussed for decades. Reports on the effect of paternal age on aneuploidy conditions have given way to broader investigations and discussions. Hassold et al. (2007), believe that paternal age is the causal factor for the appearance of fetuses with 5-10% trisomy. In recent literature, several points of view are reported that associate paternal age and chromosomal aneuploidy. De Souza et al (2010) highlighted the weak association of paternal age, while Steiner et al (2015) proposed an inverse relationship between paternal (parental) age associated with aneuploidy. It has been estimated that approximately 5-10% of trisomies have an effect proportional to paternal age, but age analysis has been limited to age groups around 40 years (Zaragoza et al 1994, Hook et al 1984, Hook et al 1990). Objective limited evidence from epidemiological genetics to correlate the confounding factor of paternal age on chromosomal aneuploidies. This left room for the analysis of paternal age as a confounding factor for chromosomal aneuploidies. MATERIAL AND METHODS This is a retrospective study. Data include one autosomal trisomy, one Down syndrome (DS), and two sex chromosome aneuploidies, one each of Turner syndrome (TS) and one Klinefelter syndrome (KFS) obtained during extensive graduate research programs over the years from 2000 to 2010 at St. John's Faculty of Medicine, Bangalore. The paternal age of all cases at conception was quantified in Excel. Paternal age at conception was the independent variable and were dichotomized into two groups: group 1 was aged ≤ 30 years and group 2 was aged > 30 years. The upper paternal age limit was 65 years. Children born in these paternal age groups were cytogenetically confirmed with DS, TS, and KFS. Dichotomized paternal age was quantified in EXCEL and linear regression analysis for r2 was applied and calculated and the p value for significance of r was applied and calculated. Results In the present study, the paternal age of 394 [155 SD-male, 40KFS, 127-DS females and 71 TS cases] confirmed chromosomal aneuploidies were observed at the time of conception. Autosomal aneuploidies [DS] were more numerous than sex chromosomal aneuploidies [KFS and TS] taken together. The number of children born with chromosomal aneuploidies was plotted against Group 1 paternal age (≥ 30 years) in Figure 1. There were 67 male DS, 16 KFS, 60 female DS, and 35 TS children in this paternal age group. . Live births with autosomal trisomy (trisomy 21) and monosomy X (TS) were significantly more numerous than with sex chromosome trisomy (KFS). The interesting observation is that there were significantly higher numbers of aneuploidies between paternal ages of 27-30 years. Figure 2 Group 2 (< 30 years) shows that the number of aneuploidies trended high between 31 and 40 years of paternal age, but decreased with advancing age. There were 88 male DS, 24 KFS, 67 female DS and 36 TS children in this paternal age group. The presence of trisomy 21 (DS) and monosomy X was greater than KFS. The coefficient of correlation determination analyzed via linear regression was tabulated in a single table. A strong positive correlation was found between group 1 (≤ 30 years) with autosomal aneuploidy (trisomy 21) for both male and female DS children and monosomy X. Sex chromosome trisomy (KFS) reflected a marginal correlation. Group 2 (>30 years) showed a significant negative correlation with the incidence of chromosomal aneuploidies. The rationale for the negative correlation may be due to children with limited aneuploidies in group 2, mainly after 45 years of age. Discussion The present study was designed to explore the correlation between paternal age and chromosomal aneuploidies, Down, Turner and Klinefelter syndromes (DS, TS, KFS). An unusual factor was noted in the study: there is a potential age effect that exists for younger paternal age with the birth of DS and TS compared to KFS. Down syndrome (trisomy 21) 90% of meiotic I errors during oogenesis in older women have a strong association with DS, whereas they represent only 5% for spermatogenesis. A strong association with meiotic error I and II during spermatogenesis and paternal age was noted. (Peterson et al 1993, Nicolaidis et al 1998, Sherman et al 1991). Most previous studies reflect that advanced paternal age, even if minimal, can be considered a risk factor for DS (Mclntosh et al 1995, Hook et al 1984). Very limited studies had an inversely proportional view that even younger paternal age may have a risk of fathering a child with DS, for example, fathers aged <20 years (14). The observations in the present study reflect the significantly higher risk of fathering a Down's child at a younger paternal age. Research studies on the effect of parental age on sex chromosome aneuploidies indicate that paternal advance can result in 0.2% of live births with sex chromosome aberrations. In the present study, the age of parents of chromosomal aneuploidies of two sexes - Klinefelter and Turner syndromes was observed. Klinefelter syndrome (47, XXY) The paternal contribution to the cause of KFS is approximately 50% (Wyrobek et al 2000). Klinefelter syndrome affects approximately 1 in 500 male births and is the most common cause of male infertility in humans. There were conflicting opinions on the effect of paternal age on KFS. Most studies believe that paternal age has an insignificant contribution on the occurrence of KFS. (Jacobs et al 1988, Thomas et al 2000). There are studies that report an alternative view. An example to cite is that of Lorda-Sanchez et al. (1992), demonstrating a correlation,.