Acontiguous gene syndrome (CGS), also known as a contiguous gene deletion syndrome, is a clinical phenotype caused by a chromosomal abnormality, such as a deletion or duplication that removes several genes lying in close proximity to one another on the chromosome. The combined phenotype of the patient is a combination of what is seen when any individual has disease-causing mutations in any of the individual genes involved in the deletion. While it can be caused by deleted material on a chromosome, it is not, strictly speaking, the same entity as a segmental aneuploidy syndrome. A segmental aneuploidy syndrome is a subtype of CGS that regularly recur, usually due to non-allelic homologous recombination between low copy repeats in the region.[1] Most CGS involve the X chromosome and affect male individuals.[2]
One of the earliest and most famous examples of a CGS involves a male patient with Duchenne muscular dystrophy (DMD), chronic granulomatous disease (CGD), retinitis pigmentosa and intellectual disability. When it was discovered that an X chromosome deletion (specifically Xp21) was the underlying cause of all of these features, researchers were able to use this information to clone the genes responsible for DMD and CGD.[1]
One of those more common CGS involves a deletion on the X chromosome (near Xp21) that encompasses DMD (causing Duchenne muscular dystrophy), NROB1 (causing X-linked adrenal hypoplasia congenita) and GK (causing glycerol kinase deficiency). These patients will have all the common features of each individual disease, resulting in a very complex phenotype.[2] Deletions near the distal tip of the p arm of the X chromosome are also a frequent cause of CGS. In addition to the previously described CGS that occur on the X chromosome, two other common syndromes are Langer–Giedion syndrome (caused by deletions of TRPS1 and EXT1on8q24 and WAGR syndrome (caused by deletions on 11q13 encompassing PAX6 and WT1.)[1]
