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Genetics Home Reference: your guide to understanding genetic conditions
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Russell-Silver syndrome

Reviewed April 2008

What is Russell-Silver syndrome?

Russell-Silver syndrome is a growth disorder characterized by slow growth before and after birth. Babies with this condition have a low birth weight and often fail to grow and gain weight at the expected rate (failure to thrive). Head growth is normal, however, so the head may appear unusually large compared to the rest of the body. Affected children are thin and have poor appetites, and some develop low blood sugar (hypoglycemia) as a result of feeding difficulties. Adults with Russell-Silver syndrome are short; the average height for affected males is about 151 centimeters (4 feet, 11 inches) and the average height for affected females is about 140 centimeters (4 feet, 7 inches).

Many children with Russell-Silver syndrome have a small, triangular face with distinctive facial features including a prominent forehead, a narrow chin, a small jaw, and down-turned corners of the mouth. Other features of this disorder can include an unusual curving of the fifth finger (clinodactyly), asymmetric or uneven growth of some parts of the body, and digestive system abnormalities. Russell-Silver syndrome is also associated with an increased risk of delayed development and learning disabilities.

How common is Russell-Silver syndrome?

The exact incidence of Russell-Silver syndrome is unknown, but the condition is estimated to affect 1 in 75,000 to 100,000 people.

What are the genetic changes related to Russell-Silver syndrome?

The genetic causes of Russell-Silver syndrome are complex. The disorder often results from the abnormal regulation of certain genes that control growth. Research has focused on genes located in particular regions of chromosome 7 and chromosome 11.

People normally inherit one copy of each chromosome from their mother and one copy from their father. For most genes, both copies are expressed, or "turned on," in cells. For some genes, however, only the copy inherited from a person's father (the paternal copy) is expressed. For other genes, only the copy inherited from a person's mother (the maternal copy) is expressed. These parent-specific differences in gene expression are caused by a phenomenon called genomic imprinting. Both chromosome 7 and chromosome 11 contain groups of genes that normally undergo genomic imprinting. Abnormalities involving these genes appear to be responsible for many cases of Russell-Silver syndrome.

Researchers suspect that at least one third of all cases of Russell-Silver syndrome result from changes in a process called methylation. Methylation is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA. In genes that undergo genomic imprinting, methylation is one way that a gene's parent of origin is marked during the formation of egg and sperm cells. Russell-Silver syndrome has been associated with changes in methylation involving the H19 and IGF2 genes, which are located near one another on chromosome 11. These genes are thought to be involved in directing normal growth. A loss of methylation disrupts the regulation of these genes, which leads to slow growth and the other characteristic features of this disorder.

Abnormalities involving genes on chromosome 7 also cause Russell-Silver syndrome. In 7 percent to 10 percent of cases, people inherit both copies of chromosome 7 from their mother instead of one copy from each parent. This phenomenon is called maternal uniparental disomy (UPD). Maternal UPD causes people to have two active copies of maternally expressed imprinted genes rather than one active copy from the mother and one inactive copy from the father. These individuals do not have a paternal copy of chromosome 7 and therefore do not have any copies of genes that are active only on the paternal copy. In cases of Russell-Silver syndrome caused by maternal UPD, an imbalance in active paternal and maternal genes on chromosome 7 underlies the signs and symptoms of the disorder.

In at least 40 percent of people with Russell-Silver syndrome, the cause of the condition is unknown. It is possible that changes in chromosomes other than 7 and 11 may play a role. Researchers are working to identify additional genetic changes that underlie this disorder.

Related Chromosome(s)

Changes involving these chromosomes are associated with Russell-Silver syndrome.

  • chromosome 7
  • chromosome 11

Related Gene(s)

Changes in these genes are associated with Russell-Silver syndrome.

  • H19
  • IGF2

Can Russell-Silver syndrome be inherited?

Most cases of Russell-Silver syndrome are sporadic, which means they occur in people with no history of the disorder in their family.

Less commonly, Russell-Silver syndrome can run in families. In some affected families, the condition appears to have an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means one copy of a genetic change in each cell is sufficient to cause the disorder. In other families, the condition has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of a gene are altered in each cell. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of Russell-Silver syndrome?

These resources address the diagnosis or management of Russell-Silver syndrome and may include treatment providers.

  • Gene Review: Russell-Silver Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1324/)
  • Genetic Testing Registry: Russell-Silver syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0175693)
  • MedlinePlus Encyclopedia: Russell-Silver syndrome (http://www.nlm.nih.gov/medlineplus/ency/article/001209.htm)

You might also find information on the diagnosis or management of Russell-Silver syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/russell-silver-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/russell-silver-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Russell-Silver syndrome?

You may find the following resources about Russell-Silver syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Russell-Silver syndrome?

  • RSS
  • Silver-Russell Dwarfism
  • Silver-Russell syndrome
  • SRS

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Russell-Silver syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Russell-Silver syndrome?

autosomal ; autosomal dominant ; autosomal recessive ; cell ; chromosome ; clinodactyly ; digestive ; digestive system ; disabilities ; DNA ; dwarfism ; egg ; epigenetic ; expressed ; failure to thrive ; gene ; gene expression ; hemihyperplasia ; hypoglycemia ; imprinting ; incidence ; inherit ; inheritance ; inherited ; intrauterine growth retardation ; IUGR ; maternal ; methyl ; methylation ; pattern of inheritance ; recessive ; sperm ; sporadic ; syndrome ; uniparental disomy

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Abu-Amero S, Monk D, Frost J, Preece M, Stanier P, Moore GE. The genetic aetiology of Silver-Russell syndrome. J Med Genet. 2008 Apr;45(4):193-9. Epub 2007 Dec 21. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18156438?dopt=Abstract)
  • Eggermann T, Eggermann K, Schönherr N. Growth retardation versus overgrowth: Silver-Russell syndrome is genetically opposite to Beckwith-Wiedemann syndrome. Trends Genet. 2008 Apr;24(4):195-204. doi: 10.1016/j.tig.2008.01.003. Epub 2008 Mar 7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18329128?dopt=Abstract)
  • Eggermann T, Schönherr N, Meyer E, Obermann C, Mavany M, Eggermann K, Ranke MB, Wollmann HA. Epigenetic mutations in 11p15 in Silver-Russell syndrome are restricted to the telomeric imprinting domain. J Med Genet. 2006 Jul;43(7):615-6. Epub 2005 Oct 19. (http://www.ncbi.nlm.nih.gov/pubmed/16236811?dopt=Abstract)
  • Gene Review: Russell-Silver Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1324/)
  • Gicquel C, Rossignol S, Cabrol S, Houang M, Steunou V, Barbu V, Danton F, Thibaud N, Le Merrer M, Burglen L, Bertrand AM, Netchine I, Le Bouc Y. Epimutation of the telomeric imprinting center region on chromosome 11p15 in Silver-Russell syndrome. Nat Genet. 2005 Sep;37(9):1003-7. Epub 2005 Aug 7. (http://www.ncbi.nlm.nih.gov/pubmed/16086014?dopt=Abstract)
  • Hitchins MP, Stanier P, Preece MA, Moore GE. Silver-Russell syndrome: a dissection of the genetic aetiology and candidate chromosomal regions. J Med Genet. 2001 Dec;38(12):810-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11748303?dopt=Abstract)
  • Netchine I, Rossignol S, Dufourg MN, Azzi S, Rousseau A, Perin L, Houang M, Steunou V, Esteva B, Thibaud N, Demay MC, Danton F, Petriczko E, Bertrand AM, Heinrichs C, Carel JC, Loeuille GA, Pinto G, Jacquemont ML, Gicquel C, Cabrol S, Le Bouc Y. 11p15 imprinting center region 1 loss of methylation is a common and specific cause of typical Russell-Silver syndrome: clinical scoring system and epigenetic-phenotypic correlations. J Clin Endocrinol Metab. 2007 Aug;92(8):3148-54. Epub 2007 May 15. Erratum in: J Clin Endocrinol Metab. 2007 Nov;92(11):4305. (http://www.ncbi.nlm.nih.gov/pubmed/17504900?dopt=Abstract)
  • Smith AC, Choufani S, Ferreira JC, Weksberg R. Growth regulation, imprinted genes, and chromosome 11p15.5. Pediatr Res. 2007 May;61(5 Pt 2):43R-47R. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17413842?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2008
Published: July 21, 2014