The Principles of Clinical Cytogenetics - Extra Materials - Springer

192 Kathleen Kaiser-Rogers and Kathleen Rao
Fig. 18. A balanced reciprocal translocation involving the long arm of chromosomes 11 and 22 [t(11;22)(q23.3;q11.2)].
This is the first recurring constitutional translocation reported in multiple, apparently unrelated families.
site. Illegitimate (nonhomologous) recombination between the resulting double-stranded breaks, perhaps
secondary to some existing repair mechanism, is then predicted to produce the recurring (11;22)
translocation. Only future studies will determine whether this current model for the formation of the
(11;22) translocation is accurate.
The presence of multiple families with the same (11;22) translocation has made it possible to
obtain good empiric data concerning viable segregants, expected phenotypes, and the various risks
associated with this rearrangement. We know, for example, that a carrier’s empiric risk for having a
liveborn child with an unbalanced karyotype is 2–10% (106,107). We also know that the unbalanced,
liveborn offspring of (11;22) translocation carriers inevitably have 47 chromosomes: 46 normal chromosomes
plus an extra or supernumerary chromosome representing the derivative chromosome 22.
These individuals are therefore trisomic for the distal long arm of chromosome 11 and the proximal
long arm of chromosome 22. Mental retardation, congenital heart disease, malformed ears with preauricular
skin tags and /or pits, a high arched or cleft palate, micrognathia, anal stenosis or atresia, renal
aplasia or hypoplasia, and genital abnormalities in males are common features shared by these unbalanced
(11;22) segregants.
Balanced carriers of the (11;22) translocation are phenotypically normal, with one possible exception.
There is a single, unconfirmed report in the literature indicating that female carriers might have
a predisposition to breast cancer (108). Although, cytogenetically the breakpoints involved in this
translocation appear to be identical to those identified in the acquired chromosome rearrangements
seen in Ewing’s sarcoma, peripheral neuroepithelioma, and Askin tumor, molecular studies have
shown that they differ (109–111) (see also Chapter 16). The gene(s) and mechanisms responsible for
the development of these neoplasms therefore have provided no clues regarding the etiology of breast
cancer development in these patients.
The (4;8)Translocation
At least 18 unrelated families with similar (4;8) translocations, or a chromosome derived from this
translocation, have been reported in the literature (7,112,113). In each case, the breakpoints involved
appear to correspond to bands 4p16 and 8p23. Most of these families have been ascertained secondary
to the birth of a clinically abnormal child with the derivative chromosome 4, but not the complementary
abnormal chromosome 8. These children are monosomic for distal chromosome 4 short arm material
and trisomic for a small amount of distal chromosome 8 short arm material. Despite the presence of 8p
trisomy, these patients are clinically indistinguishable from Wolf-Hirshhorn patients with pure 4p deletions
(see Table 1) (112). Both groups of patients demonstrate mental retardation, poor growth, hypotonia,
heart defects, and an abnormal facies, including hypertelorism, prominent forehead, broad nasal
bridge, large downturned mouth, cleft lip and/or palate, micrognathia, and dysplastic ears.