The XYY syndrome is an aneuploidy of the sex chromosomes in which a human male receives an extra Y chromosome, producing a 47,XYY karyotype. This chromosomal anomaly occurs in one of 1,000 live male births in the general population, but more frequent in infertile populations 1. In the majority of cases the phenotypic features remain normal, which hampers further management based on the specific requirements associated with a specific etiology. However, 47,XYY boys have an increased risk of behavior problems, increased growth velocity during earliest childhood, with tall stature, mild learning disability, and delayed speech and language skills 2. We herein report four cases showing XYY syndrome out of 132 infertile male subjects investigated.

The existence of a genetic component to human infertility has been suggested, although neither the specific abnormalities involved, nor their genetic mechanism of transmission, are completely defined. The present report aimed to present four cases of male patients who admitted to the genetic and fertility unit at Mansoura University Hospital because of infertility problems. Cytogenetic analysis using GTG-banding technique revealed the karyotype 47,XYY among all patients. Although cytogenetic analyses are sometimes tedious, they are very important for the identification of a variety of syndromes. Additionally, the success of providing a clinical diagnosis with cytogenetic techniques can be improved using FISH and other complementary molecular biology techniques. The latter coupled with conventional karyotying, can largely overcome the limitations of conventional banding in the accurate diagnosis and interpretation of subtle or complex chromosomal abnormalities. With both approaches, a definitive diagnosis of a 47,XYY chromosomal disorder was achieved in our study. The information obtained by such techniques provides a basis for deciding the necessary clinical management and genetic counselling of patients who require this service.

The medical history of all patients was unremarkable. There was no familial history of congenital malformation nor of exposure to drugs or toxic environmental agents. Routine analyses showed no infectious cause for their infertility. Testosterone levels are normal in 47,XYY males 5, but patients in our study had low to normal testosterone level and high to normal levels of FSH and LH. Semen analysis showed abnormal profile. Semen abnormalities may result from multiple causes such as Y chromosome microdeletions and CFTR gene mutations 67, but none of these was found in any of the four patients.

It was hypothesised that human male subfertility may have a familial component 8. From the data presented, it appears that infertility may have a genetic basis since all the four patients came from families with consanguinity marriage, but it was out of the scope of this report to evaluate the relationship between consanguinity and this chromosomal anomaly or the possibility that consanguinity may influence the phenotypic characteristics. In general, 47,XYY is not inherited, but usually occurs as a random error in chromosome separation during the formation of sperm cells, leading to formation of sperm cells with an extra copy of the Y chromosome. If one of these peculiar sperm cells contributes to the genetic makeup of a child, the child will have an extra Y chromosome in each of the body's cells 9. In some cases, the addition of an extra Y chromosome results from nondisjunction during cell division during a post-zygotic mitosis in early embryonic development. This can produce 46,XY/47,XYY mosaics 9.

Cytogenetic abnormalities have been known to be important causes of male infertility for decades and chromosomal abnormalities are more frequently observed in the population of azoo- and/or oligozoospermic males than in the general population. Men with a 47,XYY karyotype are generally fertile and there is no evidence of transmission of the extra Y chromosome to their progeny because the supernumerary Y-chromosome is eliminated during meiosis; and some XYY germ cells can complete meiosis and produce mature aneuploid sperm 10. However, they are seen more frequently in infertile populations. In this report all patients with 47,XYY karyotype are infertile. However, generalizations cannot be made regarding the correlation between karyotype and infertility phenotype. This finding may be coincidental. No systematic studies have been published showing that the XYY syndrome is associated with increased frequency of infertility. Only a few case reports of abnormalities of fertility have been published in males with the XYY syndrome 11. Nonetheless, the relatively high prevalence of this abnormal karyotype in infertile men in our report justifies the use of karyotyping to evaluate males with reproductive abnormalities especially in the case of those with high degrees of consanguinity.

FSH: follicle stimulating hormone; FISH: fluorescence in situ hybridization; GTG: G-banded using trypsin and Giemsa; LH: luteinising hormone

Written informed consent was obtained from the patients for publication of this report.

The authors declare that they have no competing interests.

FED performed cytogenetic analysis and acquisition of data. HE contributed to the analysis, review of literature and wrote the paper. Both authors read and approved the final manuscript.