Molecular cytogenetic characterisation of a complex 46,XY,t(7;8;11;13) chromosome rearrangement in a patient with Moebius syndrome

Editor—Carriers of de novo balanced reciprocal translocations and inversions have an increased risk of approximately 6% for developing multiple congenital abnormalities (MCA) and/or mental retardation (MR), compared to a 2-3% risk overall in newborn populations.1 2 Cytogenetically cryptic deletions or physical disruption or inactivation of a gene(s) in one or both breakpoint regions may account for the observed phenotypes.3 4 It seems plausible to assume that the risk for MCA/MR may be even higher in carriers of de novo complex chromosome rearrangements (CCRs), which involve at least three different chromosomes and breakpoint regions. Extreme cases involving up to seven chromosomes and 10 breakpoints have been described.5-7Indeed, most reported CCRs are associated with MCA/MR.8 9In addition, they have been found in infertile men10 and in women suffering from multiple miscarriages.11 12 The complex nature of CCRs renders karyotype interpretation by classical chromosome banding alone difficult. In many cases fluorescence in situ hybridisation (FISH) will be the best method to delineate the underlying chromosome rearrangements.7 13Here we have applied conventional FISH with chromosome painting probes and region specific large insert clones, comparative genomic hybridisation (CGH),14 15 and spectral karyotyping (SKY)16 17 to an apparently balanced and very complex rearrangement in a profoundly retarded patient with Moebius syndrome (MBS, MIM 157900).18 MBS is characterised by congenital paralysis of the seventh cranial nerve leading to facial diplegia.19 Other cranial nerves may also be affected. In addition, orofacial and limb malformations, defects of the musculoskeletal system, and MR may occur. This patient, who has classical Moebius syndrome, has been reported previously.4 He was the third child born to a 35 year old father and a 32 year old mother. Because of paresis of the facial muscles as a …