Balkan Journal of Medical Genetics

Reciprocal translocations of autosomal chromosomes are relatively common in the general population, usually without phenotypic expression in the carrier. They are usually detected after an unbalanced segregation in a carrier’s offspring occurs, or if one or both breakpoints of the translocation involve active genes.

There are many reports on the structural rearrangements of chromosome 5. The breakpoint of the short arm of chromosome 5 can be variable, extending from p13 to p15. The possible reason for the breakage of this part of chromosome 5 is a large number of repetitive elements in this region [6].

Efforts to make a genotype-phenotype map of this region have been made in order to elucidate the smallest region that is responsible for mental retardation and dysmorphic features [4,7,8]. Criteria for classification of eight types of CdCS have been suggested by some authors, depending on the breakpoints and the length of the deleted region [9].

Although the deletion of 5p is a common finding in cases with CdCS, the percentage of translocation (both de novo or familial) is not negligible (8-15%). Familial translocation occurs in 3% of all cases with CdCS. Many chromosomes are reported to be involved in a translocation together with chromosome 5. Case reports with translocations involving chromosomes 3q, 4p, 4q, 6q, 7p, 8p, 9p, 9q, 11q, 12q, 14q, 15q, 18p, 18q, and 22q have been published [10-30]. Chromosomes 10, 13, and 21, however, are the most frequently involved [3,31-37].

To the best of our knowledge, there is only one case, described by Monteleone et al. [19], with rearrangements between chromosomes 5 and 9, as in our family. In the literature concerning monosomies/trisomies 5p, significant excess of monosomic cases can be found, in comparison with trisomic cases. This is in concordance with the epistatic hypothesis for partial trisomies of chromosomes of group B. According to this hypothesis, trisomic fetuses derived from unbalanced familial translocations rarely survive the full gestational period, and are lost during the first few months of pregnancy [38].

Our case belongs to a very rare group with cases of both partial trisomy and partial monosomy 5p in the same family. Appearance of an unbalanced complement in an offspring of a balanced carrier is, according to some authors, a risk as high as 20% [39]. Sometimes, as in the above described family, this risk is even higher. The reported family had only two phenotypically normal children, but both were carriers of the translocation. Thus, a balanced translocation in the mother presented a very high risk for unbalanced offspring in this family. Such unbalanced translocations probably also occurred in the three deceased children, which will raise the risk in this family to 71% (5/7). The other two girls carry balanced translocations inherited from the mother, which further increases the risk for the next generations. There was no possibility of performing larger investigation of the karyotype in the mother’s family, so the question as to whether her translocation was de novo or inherited remains unclear.

An additional question regarding the mother's balanced translocation 5;9 and thyroid cancer can be raised. Thus far, there is no data that breakpoints involved in the balanced translocation in this patient (5p14 and 9p24) could be associated with some of the cases with thyroid carcinogenesis. However, it remains to be elucidated in the future.

Due to the high risk to the offspring in families with translocations involving chromosome 5, genetic counseling is warranted. Parents should be informed about the possibilities of prenatal diagnosis, as well as other possibilities of conception that will decrease the risk.