The Silver-Russell syndrome (SRS) is generally sporadic, but with sufficient reported cases of dominant and recessive patterns of inheritance to suggest a genetic cause in some cases, at least. No consistent cytogenetic abnormalities have been found although some features of the syndrome have been reported to be associated with structural abnormalities of distal 15q. More recently it has been shown that about 10% of SRS patients have maternal uniparental disomy of chromosome 7 which suggests the presence of a maternally imprinted gene on chromosome 7 that is associated with SRS. In the majority of patients with normal biparental inheritance of chromosome 7 the same gene could be involved if the paternal copy were deleted or mutated so that it is disabled and the maternal copy is silent because of the imprinting.

Patients with Silver‐Russell syndrome display intrauterine growth restriction and other dysmorphic features. No single genetic cause for this syndrome has been found, although there are a small number of familial cases and some patients with chromosomal rearragements. Maternal uniparental disomy of chromosome 7 has been found in approximately 7% of patients with Silver‐Russell syndrome. In five of these patients exhibiting maternal uniparental disomy, no common regions of isodisomy were found, thereby ruling out the expression of a recessive allele. It is most likely that one or more imprinted genes are responsible for the phenotype of Silver‐Russell syndrome. Human chromosome 7 demonstrates homology with two imprinted regions on mouse chromosomes 6 and 11, which are equivalent to human chromosome regions 7q32 and 7p11–p13, respectively. We directly analysed the imprinting status of candidate genes from chromosome 7 that mapped to homologous imprinted regions in the mouse and also had a potential role in growth. The candidates were the genes that encode the epidermal growth factor receptor and the insulin‐like growth binding proteins‐1 and ‐3. All three of these candidate genes are localized to chromosome region 7p11–p13. Using intragenic polymorphisms as markers, we found that all three genes showed biallelic expression in different fetal tissues. Therefore, it is unlikely that these candidate genes are directly involved in producing the phenotype of Silver‐Russell syndrome. Other candidates are under analysis, including two newly identified genes that are known to be imprinted.