What is the Evidence for Causal Epigenetic Influences on the Silver–Russell Syndrome Phenotype?

Abstract

Clinical definition of Silver–Russell sydrome In 1953 the American pediatrician Henry Silver reported two children with low birthweight, postnatal growth restriction and growth asymmetry [1]. Without knowing of these two cases, in the following year, Alexander Russell from the UK described five similar cases [2]. This group of patients became known as having Silver–Russell syndrome (SRS) or, in the US, Russell–Silver syndrome [OMIM: 180860]. Since these initial reports, several hundred cases have been described in the literature. A predominantly sporadic condition, common features include preand post-natal growth restriction, relative macrocephaly, growth asymmetry and a characteristic facial appearance. The condition is phenotypically variable, making confident clinical diagnosis difficult in some cases [3,4]. Thus in 1999, based on their ana lysis of 57 cases, Price and colleagues proposed a set of clinical diagnostic criteria, at least four of which should be present for a diagnosis of ‘classical SRS’: birthweight >2 SD below the mean, short stature at the time of diagnosis, weight >2 SD below the mean; limb, body or facial asymmetry and fifth finger clinodactyly [5].