The Cat eye syndrome (CES), also termed the Schmid–Fraccaro syndrome, is a severe disorder in which individuals have multiple birth defects such as congenital heart abnormalities, renal malformations, craniofacial anormalies, male genital anomalies, skeleton defects, borderline to moderately severe mental retardation, and cat-like downward-slanted openings between the upper and lower eyelids. CES is commonly associated with a tetrasomy (i.e. four gene copies, one from each normal chromosome, two from the sSMC) or, less commonly, trisomy (three gene copies, one from each normal chromosome and one from the sSMC) of the entire p arm of chromosome 22 plus a small part (i.e. G bands 1 through 11) of this chromosome's q arm. A chromosomal rearrangement mutation between the paired chromosomes 22 occurring during the miosis cell divisions that produce a parent's sperm or egg forms a CES-associated sSMCs that is passed to the parent's offspring. Rarely, CES results from a balanced translocation between a parent's paired chromosome 22. A balanced translocation is an even exchange between two chromosomes that results in no change in genetic information and generally has no detrimental effects on its carriers. However, a parent with a balanced translocation in chromosomes 22 has an increased risk of having a child with CES; this is due to a chromosomal rearrangement mutation between the balanced chromosomes 22 that forms a sSMC-associated sSMC in the parent's sperm or egg and is passed to the parent's offspring. Finally, in extremely rare cases a parent may carry a CES-associated sSMC in only some of their cells due to mosaicism, have little of no CES defects, and directly transmit this sSMC through their sperm or eggs to their offspring. A CES-associated sSMC may be small, large, or ring-shaped and typically includes 2 Mb, i.e. 2 million DNA base pairs, termed the CES critical region, located on its q arm at bands 11.1 through ll.23. This area contains the CECR1, SLC22A18, and ATP6V1E1 genes which are strong candidate genes for causing or promoting at least some of the birth defects in CES.
