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Useful Terminology/Concepts

The following is a compilation of useful terminology/concepts (in CES context) to those interested in the details of CES:

  • Small supernumerary marker chromosome (sSMC): these chromosomes are present in addition to the ‘normal’ 46. In CES the marker chromosome arises from chromosome 22 and the majority of individuals are observed to carry a sSMC [1].
  • Gene overexpression: abnormally high production of a protein encoded by a particular gene due to a problem in the gene regulation mechanism.
  • Karyotype analysis: profiling of an individual’s chromosomes by size, type, and quantity to determine the presence of chromosomal abnormalities.

Case Studies

1. A case study done by Kvarnung in 2005 describes a family with all the siblings displaying phenotypes of CES. After conducting FISH analysis it was discovered the severity of the phenotypes being displayed correlated to the number of cells containing genes with a duplicated proximal part of chromosome 22q1 (the chromosome causing CES). For example, one of the children displayed no CES phenotypes when 32% of the epithelial cells contained a duplicated chromosome 22, while a sibling with 47% of the epithelial cells containing a duplicated chromosome 22 had moderate micropthalmia, an incomplete coloboma of the iris and preauricular pits. The study also found that some tissue types displayed a higher number of cells with a duplicated region of chromosome 22 compared to others. In this study, epithelial cells had a higher frequency of duplicated chromosome 22 regions compared to blood cells. Germ cells, however, were found to show the greatest frequency in duplicated chromosome 22. Therefore investigations of germ cells by FISH was found to be the best day to look for germline mosaicsm. [2]

Key Points:

  • With the transmission of mosaicsm for a duplicated chromosome 22 regions responsible for CES, the degree of CES phenotypes varied amongst offspring due to different frequency of mosaicsm. [2]
  • Epithelial cells had a higher frequency of cells with a duplicated chromosomes 22 region compared to blood cells with the spermatozoa of the father having the highest frequency. [2]
  • Genetic investigations by FISH analysis of germ cells of mother and father can help determine the risk for parents of a child with CES. [2]


2. A study by Belangero et. al investigating the phenotypic variability of CES followed the development and progression of Cat Eye Syndrome in seven afflicted individuals. Three of the seven were related: two children and their maternal mother. The family had no previous history of CES and all carried the Type 1 marker chromosome. There were no similarities in the phenotypes between any of the individuals. A body mass of equal to or less than 50% percentile was observed in all children [5]. The most common phenotype observed was the presence of preauricular tags/pits while the most common “major” phenotype was some form of heart defect. Belangero et al. suggested that epistasis may be the source of such great phenotypic variability in CES patients [5].

Key points:

  • It is suggested that future studies should include CES screening in the individual’s immediate family to determine the linkage between genetic inheritance and disorder manifestation [5].
  • The delicacy in CES diagnosis is emphasized by this study: those with multiple symptoms found in individuals with CES may benefit from cytogenetic analysis.
  • Epistasis may be the source of the phenotypic variability in CES patients [5].

Critical regions for CES

The critical region for CES is located on Chromosome 22 and is known to be less than 3.6Mb long [3]. The identification of the critical region has allowed researchers to begin identifying CES candidate genes.

Recently, the 3.6Mb region was further narrowed down to 2Mb by examining case studies of those with CES for chromosomal similarities. Researchers were able to identify 14 putative genes in the region [4]. Once located, these genes can distinguished from others by the “CESCR” (Cat Eye Syndrome Critical Region) naming. The putative genes were investigated for synteny: 10 of these exhibited synteny. Some of these putative genes are being further investigated through mice to determine if they are involved in the expression of CES symptoms.

Furthermore, the location of the critical region, near locus D22S36, has helped distinguish those with CES from those with DiGeorge Syndrome [3].



2. Kvarnung, et al., (2012). Inherited mosaiscm for the supernumerary chromosome in cat eye syndrome: inter and intra-individual variation and correlation to the phenotype.

3. McDermid, H.E., et al. (1996). Long-range mapping and construction of a YAC contig within the Cat Eye Syndrome critical region. 6(12), August 03, 2012. 1149-1159

4. Footz, T.K., et al. (2001). Analysis of the Cat Eye Syndrome critical region in humans and the region of conserved synteny in mice: a search for candidate genes at or near the human chromosome 22 pericentromere. 11(6), August 05, 2012. 1053-1070.

5. Belangero, S.I., et al. (2012). Wide clinical variability in Cat Eye Syndrome patients. 138, September 30, 2012. 5-10.