Silver-Russell syndrome

Silver-Russell syndrome is a rare genetic disorder characterized by slow growth before and after birth, often leading to a low birth weight and distinctive physical features. It can also involve feeding difficulties, metabolic problems, and developmental delays.

Overview

Silver-Russell syndrome is a rare disorder characterized by slow growth before and after birth. Babies with this condition typically have a low birth weight and often do not grow and gain weight at the expected rate (failure to thrive). Head growth is normal, however, so the head may appear large compared to the rest of the body. In some affected individuals, one side of the body may be bigger than the other.

Symptoms & Features

Affected children often have difficulty feeding. Some children develop recurrent episodes of low blood glucose (hypoglycemia). Gastrointestinal problems, such as vomiting and a backflow of stomach acid into the esophagus (called gastroesophageal reflux or GERD), are also common.

Adults with Silver-Russell syndrome are typically shorter than average and may have an increased risk of developing metabolic problems such as type 2 diabetes (the most common form of diabetes). Affected individuals often have asymmetric or uneven growth of certain parts of the body, such as the arms and legs. Additional skeletal features may include an unusual curving of the fifth finger, short fingers, and abnormal curvature of the spine.

Many people with Silver-Russell syndrome have a small, triangular face with distinctive features, including a prominent forehead, a small jaw, a pointed chin, and downturned corners of the mouth.

Other features can include the delayed development of motor skills, speech and language problems, and learning disabilities.

Frequency

It is estimated that 1 in 30,000 to 1 in 100,000 people in the world have Silver-Russell syndrome.

Causes & Risk Factors

The genetic causes of Silver-Russell syndrome are complex. The disorder is often the result of the abnormal regulation of genes that control growth. These genes are located in particular regions of chromosome 7 and chromosome 11.

Most cases of Silver-Russell syndrome are caused by changes in chromosome 11 that affect the regulation of specific genes. The genes that are thought to play the most significant role in Silver-Russell syndrome are the H19 and IGF2 genes. Disruption of the activity of these genes leads to slow growth and the other characteristic features of Silver-Russell syndrome.

When Silver-Russell syndrome is caused by problems that involve chromosome 7, it is primarily due to issues with the inheritance of the chromosome. Specifically, Silver-Russell syndrome can occur when both copies of chromosome 7 are derived from the egg cell. Normally, this does not affect gene activity, but some genes only work when they are derived from the egg cell or from the sperm cell. When both copies of chromosome 7 are derived from the egg cell, affected individuals may have two active copies of some genes and no active copies of other genes. This dysregulation of gene activity results in the signs and symptoms of Silver-Russell syndrome.

Rarely, variants (also called mutations) in a single gene cause Silver-Russell syndrome. These genes include the CDKN1C, IGF2, HMGA2, and PLAG-1 genes.

In 30 to 40 percent of people with Silver-Russell syndrome, the cause of the condition is unknown. Researchers are working to identify additional genetic changes that cause this disorder.

Inheritance

Most cases of Silver-Russell syndrome result from a new (de novo) event that occurs during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

Rarely, Silver-Russell syndrome can run in families. In some affected families, the condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, the pattern of inheritance in a specific family depends on the exact genetic change and whether the change came from the egg cell or the sperm cell.

Other Names for This Condition

• RSS
• Russell-Silver syndrome
• Silver-Russell dwarfism
• SRS