Identifying Cryptic Translocations

The importance of identifying such cryptic translocations for accurate genetic counseling and recurrence risk assessment was highlighted by the discovery of several cryptic translocations involved in Miller-Dieker syndrome (MDS) (reviewed in (Ledbetter, 1992). MDS is a disorder characterized by lissencephaly, a neuronal migration disorder, which is due to monosomy for the region in 17p13 containing the LIS1 gene.  Although the majority of deletion events in MDS patients are de novo events with no increased recurrence risk, in 12% of cases one of the parents is found to carry a balanced translocation, thus conferring a risk of an unbalanced child as high as 50% (Dobyns et al., 1993). Since many of these translocations have escaped detection by chromosome banding analysis, it has become the standard of care to test these patients and their parents by FISH methods.

Similar cryptic translocations have been observed for other known microdeletion syndromes which map near telomeres, including 4p and 5p (reviewed in (Ledbetter, 1992). Given these findings for known microdeletion syndromes, concerns can be raised that undetected cryptic translocations for all human telomeres could represent a major cause of idiopathic mental retardation as well as unexplained miscarriages.