Silver–Russell syndrome

Silver–Russell syndrome (SRS), also called Silver–Russell dwarfism or Russell–Silver syndrome (RSS) is a growth disorder occurring in approximately 1/50,000 to 1/100,000 births. In the United States it is usually referred to as Russell–Silver syndrome, and Silver–Russell syndrome elsewhere. It is one of 200 types of dwarfism and one of five types of primordial dwarfism. Silver–Russell syndrome (SRS), also called Silver–Russell dwarfism or Russell–Silver syndrome (RSS) is a growth disorder occurring in approximately 1/50,000 to 1/100,000 births. In the United States it is usually referred to as Russell–Silver syndrome, and Silver–Russell syndrome elsewhere. It is one of 200 types of dwarfism and one of five types of primordial dwarfism. There is no statistical significance of the syndrome occurring preferentially in either males or females. Although confirmation of a specific genetic marker is in a significant number of individuals, there are no tests to clearly determine if this is what a person has. As a syndrome a diagnosis is typically given for children upon confirmation of the presence of several symptoms listed below. Symptoms are Intrauterine Growth Restriction (IUGR) combined with some of the following: The average adult height for patients without growth hormone treatment is 4'11' for males and 4'7' for females. Its exact cause is unknown, but present research points toward a genetic and epigenetic component, possibly following maternal genes on chromosomes 7 and 11. It is estimated that approximately 50% of Silver Russell patients have hypomethylation of H19 and IGF2. This is thought to lead to low expression of IGF2 and over-expression of the H19 gene. In 10% of the cases the syndrome is associated with maternal uniparental disomy (UPD) on chromosome 7. This is an imprinting error where the person receives two copies of chromosome 7 from the mother (maternally inherited) rather than one from each parent. Other genetic causes such as duplications, deletions and chromosomal aberrations have also linked to Silver–Russell syndrome. Interestingly, Silver-Russell patients have variable hypomethylation levels in different body tissues, suggesting a mosaic pattern and a postzygotic epigenetic modification issue. This could explain the body asymmetry of the SRS phenotype.