Genetic counseling in Robertsonian translocations der(13;14): Frequencies of reproductive outcomes and infertility in 101 pedigrees

Abstract

Robertsonian translocations 13/14 are the most common chromosome rearrangements in humans. However, most studies aimed at determining risk figures are more than 20 years old. Their results are often contradictory regarding important topics in genetic counseling such as infertility and unfavorable pregnancy outcomes. Here, we present a study on a sample of 101 previously unreported pedigrees of der(13;14)(q10;q10). In order to minimize problems of partial ascertainment, we included families with a wide range of reasons of ascertainment such as birth of a child with congenital anomalies, prenatal diagnosis due to maternal age, fertility problems and recurrent pregnancy loss. No evidence of increased infertility rates of female and male carriers was found. The detected miscarriage frequency of female carriers was higher than previously reported (27.6 +/- 4.0% of all spontaneous pregnancies). This may be explained by an over-correction of earlier studies, which excluded all unkaryotyped miscarriages. In three out of 42 amniocenteses, translocation trisomies 13 were diagnosed (7.1 +/- 4.0% of all amniocenteses). The frequency of stillbirths was 3.3 +/- 1.6% for female carriers and 1.4 +/- 1.4% for male carriers. A low risk for the live birth of translocation trisomy 13 children was confirmed since no live born children with trisomy 13 or Pätau syndrome were detected in the ascertainment-corrected sample.

Inheritance of a t(13;14)(q10;q10) Robertsonian translocation with a low level of trisomy 13 mosaicism

“…For live-born offspring, the risk of an unbalanced karyotype with trisomy 13 is extremely low. In their study of 101 pedigrees with der (13;14)(q10;q10), Engels et al [8] did not detect a Robertsonian translocation trisomy 13 at term, confirming previous findings. In prenatally diagnosed fetuses with a Robertsonian translocation, three out of 168 showed a mosaic trisomy, providing a risk estimate of~2% [3].…”

Preimplantation genetic diagnosis for couples with a Robertsonian translocation: practical information for genetic counseling

“…Moreover, the percentage of abnormal gametes is correlated with the proportion of abnormal embryos in translocation carriers [22,23]. The frequencies of miscarriage and stillbirth are higher in female than in male der (13;14) carriers [24]. Thus, the sex of the carrier may influence PGD results.…”

Preconceptional diagnosis for Robertsonian translocation as an alternative to preimplantation genetic diagnosis in two situations: a pilot study

“…Furthermore, PCD could also reduce miscarriage frequency, which has recently been reported to be increased and close to 30% for women heterozygous for a Robertsonian translocation [18].…”

“…The strategy that we propose may permit identification of women with a particularly high incidence of oocyte aneuploidy, as shown by our pilot series, in a population known to be associated with a variable risk. The 30% miscarriage frequency for women heterozygous for a Robertsonian translocation [18] is probably the combination of two opposite situations: women with low or high risk of chromosome malsegregation.…”