To inform clinicians about fertility in males with Down syndrome.
Medical Genetics Department of a tertiary-care hospital.
A 26-year-old man with confirmed nonmosaic trisomy 21.
Karyotype, amniocentesis, paternity testing using microsatellite markers.
Confirmed paternity in the son of a male with nonmosaic trisomy 21.
A male with nonmosaic Down syndrome fathered a normal son, and the paternity was proven by microsatellite marker analysis.
Although Down syndrome males have been reported to be infertile, it may not always be true. Infertility in males has been attributed to defective spermatogenesis, but ignorance of the sexual act may be one of the contributing factors. It is important to advise postpubertal Down syndrome males on contraceptive measures.
"In our experience, a 47,XXY pachytene has never been observed. In contrast, in cases of supernumerary autosomes, proven fertility has been described in a Down syndrome–affected male (Pradhan et al, 2006). The same is true for small supernumerary markers, which are known to not be associated with a severe alteration of spermatogenesis and which are frequently found fortuitously, even if spermatogenesis breakdown has been reported in one case (Jaafar et al, 1994). "
[Show abstract][Hide abstract] ABSTRACT: : For nonobstructive azoospermic (NOA) patients with a normal karyotype or for Klinefelter syndrome (47,XXY) patients, intracytoplasmic sperm injection is associated with an increased aneuploidy risk in offspring. We examined testicular cells from patients with different azoospermia etiologies to determine the origin of the aneuploid spermatozoa. The incidence of chromosome abnormalities was investigated in all types of azoospermia. Four study subgroups were constituted: Klinefelter patients (group 1), NOA patients with spermatogenesis failure but a normal karyotype (group 2), obstructive azoospermic patients with normal spermatogenesis (group 3), and control patients with normal sperm (group 4). The pachytene stage (in the three azoospermic groups) and postmeiotic cells (in all groups) were analyzed with fluorescence in situ hybridization. No aneuploid pachytene spermatocytes were observed. Postmeiotic aneuploidy rates were higher in the two groups with spermatogenesis failure (5.3% and 4.0% for groups 1 and 2, respectively) than in patients with normal spermatogenesis (0.6% for group 3 and group 4). Whatever the etiology of the azoospermia, the spermatozoa originated from euploid pachytene spermatocytes. These results strengthen the hypothesis whereby sperm aneuploidy in both Klinefelter patients and NOA patients with a normal karyotype results from meiotic abnormalities and not from aneuploid spermatocytes. The fact that sperm aneuploidy was more frequent when spermatogenesis was altered suggests a deleterious testicular environment. The study results also provide arguments for offering preimplantation genetic diagnosis or prenatal diagnosis when a pregnancy occurs for fathers with NOA (whatever the karyotype).
Journal of Andrology 11/2012; 33(6). DOI:10.2164/jandrol.111.016329 · 2.47 Impact Factor
"However, empiric risks are difficult to estimate, as reproduction rates are low. Males with Down syndrome are typically infertile, although there have been reports of men with Down syndrome who have fathered pregnancies (Pradhan et al. 2006). Females with Down syndrome are typically fertile and empiric data indicate a 30–50% chance of having a child with Down syndrome (Gardner and Sutherland 2004; Harper 2004). "
[Show abstract][Hide abstract] ABSTRACT: Down syndrome is one of the most common conditions encountered in the genetics clinic. Due to improvements in healthcare, educational opportunities, and community inclusion over the past 30 years, the life expectancy and quality of life for individuals with Down syndrome have significantly improved. As prenatal screening and diagnostic techniques have become more enhanced and widely available, genetic counselors can expect to frequently provide information and support following a new diagnosis of Down syndrome. This guideline was written for genetic counselors and other healthcare providers regarding the communication of a diagnosis of Down syndrome to ensure that families are consistently given up-to-date and balanced information about the condition, delivered in a supportive and respectful manner.
"It has been generally assumed that T21 DS men are infertile, but these reports suggest that at least in cases of T21 mosaicism fertility may be restored. There are also reports of two cases of apparently non-mosaic DS men, who have fathered children [49,50]. T21 DS females, on the other hand, show impaired fertility and premature menopause, but there are many more reports of offspring to apparently non-mosaic DS mothers than DS fathers [51,52]. "
[Show abstract][Hide abstract] ABSTRACT: Down syndrome (DS), characterized by an extra free chromosome 21 is the most common genetic cause for congenital malformations and learning disability. It is well known that the extra chromosome 21 originates from the mother in more than 90% of cases, the incidence increases with maternal age and there is a high recurrence in young women. In a previous report we have presented data to indicate that maternal trisomy 21 (T21) ovarian mosaicism might provide the major causative factor underlying these patterns of DS inheritance. One important outstanding question concerns the reason why the extra chromosome 21 in DS rarely originates from the father, i.e. in less than 10% of T21 DS cases. We here report data indicating that one reason for this parental sex difference is a very much lower degree of fetal testicular in comparison to ovarian T21 mosaicism.
We used fluorescence in situ hybridisation (FISH) with two chromosome 21-specific probes to determine the copy number of chromosome 21 in fetal testicular cell nuclei from four male fetuses, following termination of pregnancy for a non-medical/social reason at gestational age 14-19 weeks. The cells studied were selected on the basis of their morphology alone, pending immunological specification of the relevant cell types. We could not detect any indication of testicular T21 mosaicism in any of these four male fetuses, when analysing at least 2000 cells per case (range 2038-3971, total 11.842). This result is highly statistically significant (p < 0.001) in comparison to the average of 0.54% ovarian T21 mosaicism (range 0.20-0.88%) that we identified in eight female fetuses analysing a total of 12.634 cells, as documented in a previous report in this journal.
Based on these observations we suggest that there is a significant sex difference in degrees of fetal germ line T21 mosaicism. Thus, it would appear that most female fetuses are T21 ovarian mosaics, while in sharp contrast most male fetuses may be either very low grade T21 testicular mosaics or they may be non-mosaics. We further propose that this sex difference in germ line T21 mosaicism may explain the much less frequent paternal origin of T21 DS than maternal. The mechanisms underlying the DS cases, where the extra chromosome 21 does originate from the father, remains unknown and further studies in this respect are required.
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