Due to the atypical symptoms of 47, XYY syndrome, approximately 85% of patients are not diagnosed until they develop infertility . Most patients experienced undiagnosed in the fetus and at birth, often with delayed or missed diagnosis. It is currently believed that 47, XYY syndrome is caused by the unsegregation of Y chromosomes during meiosis II or mitosis after the formation of zygotes. In theory, X, Y, XY, YY should be observable in the sperm of such patients, and there should be a 50% chance of abnormal karyotypes occurring in their offspring. However, studies have reported that chromosomal abnormalities are rare in the offspring of such patients, and the incidence is less than 1% [9, 10]. Although the risk of infertility for this syndrome is four times higher than that of ordinary men, most patients are fertile. The reason for this phenomenon is believed to be the loss of the extra Y chromosomes before mitosis. The animal model that sterile triploid chromosome mice can obtain fertile offspring through the phenomenon of “trisomy bias chromosome loss” also strongly supports this view . Studies have shown that the sperm count of patients with 47, XYY syndrome is uncertain, and the sperm count ranges from average to azoospermia [9, 11]. Moreover, 46, XY/47, XYY chimera can produce normal sperm; most people are fertile, as we reported in this patient. Only a few patients experience fertility difficulties. Regarding these patients, percutaneous epididymal sperm aspiration (PESA) and intracytoplasmic sperm injection (ICSI) may help increase their fertility. The in vitro fertilization and embryo cleavage rates are high, and the fetuses born are also very healthy [9, 10].
CBAVD is usually found due to infertility or surgery. Its diagnostic criteria are standard or small testicular volume, untouchable vas deferens, normal seminal FSH level, and low semen volume (< 1 mL). Semen has the following characteristics: no sperm; acidic pH; undetectable fructose or low concentration. Studies have found that the incidence of seminal vesicle abnormalities such as absence, dysplasia, or cystic dysplasia in patients with CBAVD is as high as 36–92% [11,12,13]. Furthermore, studies have reported that 11–21% of patients with CBAVD have renal absences. As both the male reproductive and urinary systems originate from the mesorenal tube, the two are closely related in embryology and anatomy, which explains why malformations of the reproductive system are often associated with renal malformations .
CBAVD is considered an atypical manifestation of CF. Approximately 95% of patients with CF who only exhibit CBAVD have CFTR gene mutations. In Chinese patients, the mutation frequency of CFTR is 12.7%, and I556V is the most common type of mutation [6, 15]. The mutation spectrum is 5 T, p. Ile556Val, and p. Gln1352His (mutant allele counts are 175, 65, and 19, respectively). The most common type of mutation is a heterozygous mutation, which is significantly different from European races. Two-thirds of Caucasian CBAVD patients were identified having CFTR mutation associated with CF, but those mutations were reported to be rare in Chinese men. Besides, Caucasian patients had higher F508del mutation frequency, but I556V was the most common mutation in Chinese CBAVD patients [5,6,7]. In this case, two mutations, p.L88X and p.P750L, were found. These two mutations are not rare, but they are pathogenic.
Studies have shown that sperm production is impaired in patients with CBAVD, the risk of miscarriage and stillbirth is significantly increased, and the live birth rate is reduced considerably [5, 16]. However, many patients can produce their offspring through PESA and ICSI. To our knowledge, this article reports the first case of infertility with sex chromosomal abnormalities combined with autosomal gene mutations. Regarding eugenics, prenatal genetic counseling is necessary for both CBAVD and 47, XYY syndrome.
In conclusion, we reported a rare case who is a congenital absent of bilateral vas deferens (CBAVD) infertile patient, concomitant with 46, XY/47, XYY mosaic karyotype. Given the low genetic risk of the disease, we recommend that patients undergo intracytoplasmic sperm injection (ICSI) for fertility assessment. Genetic counseling is necessary for patients with either CBAVD or 47, XYY karyotype in their pursuit of parenthood.