Genetic counseling in carriers of reciprocal chromosomal translocations involving long arm of chromosome 16

Abstract

Families with balanced chromosomal changes ascertained by unbalanced progeny, miscarriages, or by chance are interested in their probability for unbalanced offspring and other unfavorable pregnancy outcomes. This is usually done based on the original data published by Stengel-Rutkowski et al. several decades ago. That data set has never been updated. It is particularly true for the subgroup with low number of observations, to which belong reciprocal chromosomal translocations (RCTs) with breakpoint in an interstitial segment of 16q. The 11 pedigrees from original data together with the new 18 pedigrees of RCT carriers at risk of single-segment imbalance detected among 100 pedigrees of RCT carriers with breakpoint position at 16q were used for re-evaluation of the probability estimation for unbalanced offspring at birth and at second trimester of prenatal diagnosis, published in 1988. The new probability rate for unbalanced offspring after 2 : 2 disjunction and adjacent-1 segregation for the total group of pedigrees was 4 +/- 3.9% (1/25). In addition, the probability estimate for unbalanced fetuses at second trimester of prenatal diagnosis was calculated as 2/11, i.e. 18.2 +/- 11.6%. The probability rates for miscarriages and stillbirths/early deaths were about 16 +/- 7.3% (4/25) and <2% (0/25), respectively. Considering different segment lengths of 16q, higher probability rate (0/8, i.e. <6.1%) for maternal RCT carriers at risk of distal 16q segment imbalance (shorter segment) was obtained in comparison with the rate (0/10, i.e. <4.8%) for RCT at risk of proximal segment imbalance (longer segment). It supports findings obtained from the original data for RCT with other chromosomes, where the probability for unbalanced offspring generally increased with decreasing length of the segments involved in RCT. Our results were applied for five new families with RCT involving 16q, namely three at risk of single-segment imbalance [t(8;16)(q24.3;q22)GTG, ish(wcp8+,wcp16+;wcp8-,wcp16+), t(11;16)(q25;q22)GTG, and t(11;16)(q25;q13)GTG] and two with RCT at risk of double-segment imbalance [t(16;19)(q13;q13.3)GTG, isht(16;19)(q13;q13.3) (D16Z3+,16QTEL013-D19S238E+,TEL19pR-; D16Z3-, D19S238E-,TEL19pR+), and t(16;20)(q11.1;q12)GTG, m ish,t(16;20)(wcp16+,wcp20+;wcp16+,wcp20+)]. They have been presented in details to illustrate how the available empiric data could be used in practice for genetic counseling.

Further delineation of the phenotype maps for partial trisomy 16q24 and Jacobsen syndrome by a subtle familial translocation t(11;16)(q24.2;q24.1)

“…Identical imbalances were identified in the index patient (Patient 1) and his mother's cousin (Patient 2). The presence of two unbalanced carriers in this pedigree is in accordance with the high-risk estimate of 10% for unbalanced live-born offspring for this translocation [Stasiewicz-Jarocka et al, 2004].…”

Meiotic and pedigree segregation analyses in carriers of t(4;8)(p16;p23.1) differing in localization of breakpoint positions at 4p subband 4p16.3 and 4p16.1

“…Pedigree analyses of 46 families with RCT involving 4p by Stengel-Rutkowski et al [ 6 ] showed a high risk (20.5 ± 4.6 %) of unbalanced offspring (trisomy or monosomy 4p16) for RCT carriers of shorter segments and lower risks of about 4.5 ± 2.5 % for RCT carriers at risk of longer segment imbalances. This supports the results calculated for RCT carriers with other chromosomes, where the probability of unbalanced offspring generally increases with the decreasing length of the segments involved in RCT [ 7 – 10 , 19 ].…”

“…These high probabilities rate for birth of child with chromosome imbalancy are not surprising. In general the relative high survival rates for progeny with imbalance of subterminal region of other involved chromosomes are observed in families of RCT carriers [ 2 , 7 , 19 ]. However, direct values of the probability rate for having children with unbalanced karyotype vary depending on the translocation (i.e., 18 %, compared to 42 %).…”

Risk evaluation of carriers with chromosome reciprocal translocation t(7;13)(q34;q13) and concomitant meiotic segregation analyzed by FISH on ejaculated spermatozoa

“…In the case of RCT carriers a genetic counseling should be offered and probability rates should be estimated for all particular types of pathology (unbalanced progeny at birth and at prenatal diagnosis, unkaryotyped miscarriages, stillbirth/early death newborns). This can be done on the basis of segregation analysis of pedigrees, if available [Stengel‐Rutkowski et al, 1988; Midro et al, 1992, 2000; Barisic et al, 1996; Stasiewicz‐Jarocka et al, 2004]. To assess the probability rate of the presence of unbalanced progeny, the information on given combinations of chromosome segments in the karyotype of the offspring of the individual RCT carrier, and the information about the number of normal offspring should be obtained directly from the analysis of a relative large pedigree consisted of several generations and many members.…”