The Molecular Genetics of Trisomy 18: Phenotype–Genotype Correlations

Abstract

The trisomy 18 syndrome can result from a full, mosaic, or partial trisomy 18. The main clinical findings of full trisomy 18 consist of prenatal and postnatal growth deficiency, characteristic facial features, clenched hands with overriding fingers and nail hypoplasia, short sternum, short hallux, major malformations, especially of the heart, and profound intellectual disability in the surviving older children. The phenotype of partial trisomy 18 is extremely variable. The aim of this article is to systematically review the scientific literature on patients with partial trisomy 18 in order to identify regions of chromosome 18 that may be responsible for the specific clinical features of the trisomy 18 syndrome. We confirmed that trisomy of the short arm of chromosome 18 does not seem to cause the major features. However, we found candidate regions on the long arm of chromosome 18 for some of the characteristic clinical features, and thus a phenotypic map is proposed. Our findings confirm the hypothesis that single critical regions/candidate genes are likely to be responsible for specific characteristics of the syndrome, while a single critical region for the whole Edwards syndrome phenotype is unlikely to exist.

Key Concepts:

  • The phenotype of human chromosomal syndromes is comprised of the individual component manifestations of the condition.

  • Using case descriptions of patients with partial trisomy of a segment of a chromosome, an investigator can potentially map the well‐defined and more specific phenotypic findings to a region of the chromosome. Narrowing a region allows for review of the known genes in the region and for hypothesising the causative gene(s) for the phenotype.

  • The certainty in inferring a causative region or individual gene for a component manifestation depends on the specificity and consistency of occurrence of the individual feature.

  • Correlations of phenotypes with genotypes can lead to detection of candidate genes which provide insight into disease mechanisms and ideally into the development of strategies for therapeutic intervention and prevention.

  • The findings in this paper confirm the hypothesis that single critical regions/candidate genes are likely to be responsible for specific characteristics of the syndrome, while a single critical region for the whole Edwards syndrome phenotype is unlikely to exist.

Keywords: trisomy 18; Edwards syndrome; genotype–phenotype correlation; phenotypic map; 18p duplication; 18q duplication; intellectual disability

Figure 1.

Phenotypic map of chromosome 18 based on the review of the literature.

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Peron, Angela, and Carey, John C(Nov 2014) The Molecular Genetics of Trisomy 18: Phenotype–Genotype Correlations. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0025246]