Translocation form of Wolf-Hirschhorn syndrome --assessment of recurrence rate probability.

PURPOSE

The families experienced by occurrence of child with Wolf-Hirschhorn syndrome (WHS: OMIM # 194190) and by other unfavourable pregnancy outcomes (miscarriages or stillbirths/early deaths and partial trisomy 4p imbalance leading to intellectual disability in live born progeny) are asking for genetic counseling. In order to obtain the recurrence probability rates for the particular forms of unfavourable pregnancy we collected the empirical data and evaluated pedigrees of reciprocal chromosome translocations (RCT) carriers involving 4p. Results were applied to family of carrier of t(4;11)(p16.1;q23.3) ascertained by four miscarriages, in which latter the girl with WHS was born.

MATERIAL AND METHODS

Total empirical data about 170 pregnancies of 46 carriers were collected from 25 pedigrees RCT at risk for single segment imbalance. Classification was based mostly on cytogenetic methods. The probability rates of particular type of pathology related to total number of pregnancies after ascertainment correction have been calculated according to the method of Stengel-Rutkowski and Stene.

RESULTS

The risk figures for unbalanced offspring after 2:2 disjunction and adjacent-1 segregation for whole group of pedigrees were calculated as 15.2 +/- 3.5% (16/105), for unbalanced fetuses at second trimester of prenatal diagnosis as 50 +/- 13.4% (7/14), for miscarriages about 19 +/- 3.8% (20/105) and for stillbirths/early death as 15.2 +/- 3.5% (16/105). The higher probability rate for RCT carriers at risk for distal 4p--shorter segment imbalance (28.6 +/- 12%, 4/14) in comparison to the rate for proximal (medium) one as 15.4 +/- 4.5% (10/65) and to more proximal (longer) one as 7.7 +/- 5.2% (2/26) were found.

CONCLUSIONS

Our results confirm that the recurrence probability rates are different for particular categories of unfavourable pregnancy outcomes and dependent on size and genetic content of unbalanced 4p segments.