Silver-Russell syndrome: genetic basis and molecular genetic testing

We therefore suggest a diagnostic algorithm focused on the 11p15 hypomethylation, UPD(7)mat and cryptic chromosomal imbalances for patients with typical SRS phenotype, but also with milder clinical signs only reminiscent for the disease.Over the past 20 years it has become increasingly clear that genomic imprinting is of great relevance for human diseases. Imprinted genes with a parent-of-origin specific expression are involved in various aspects of growth and behaviour that are rooted in the prenatal period and indeed, many of the so far known congenital imprinting disorders (IDs) are clinically characterised by growth disturbances. While Angelman, Prader-Willi and Beckwith-Wiedemann syndromes (BWS) are well established IDs, imprinting defects in patients with Silver-Russell syndrome (SRS) are relatively new findings.The main features of SRS [RSS; OMIM 180860] are severe intrauterine and postnatal growth retardation, relative macrocephaly and a characteristic small, triangular face. The disease is associated with additional dysmorphic features including fifth finger clinodactyly and hemihypoplasia (table 1). Although a clinical scoring system to assist the diagnosis has recently been suggested [1], the accuracy of diagnosis is influenced by the experience of the clinical investigator. Furthermore, the clinical picture of SRS in adulthood is less clear than in early childhood.The frequency of SRS is currently unknown, but it is probably underdiagnosed due to the broad range of features [1].The influence of genetic factors in the aetiology of SRS is documented by classical genetic findings such as familial cases of SRS and cytogenetic aberrations. Most cases of SRS are sporadic, but familial cases have been reported (for review: [2]). Duncan et al. [2] suggested that most familial cases were transmitted in an autosomal dominant manner with marked intrafamilial variability. An autosomal recessive inheritance has been supposed in eight families but in six of them the c