The Molecular Genetics of Trisomy 18: Phenotype– Genotype Correlations

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, andprofound 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 a 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.