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Description
Silver-Russell syndrome is a rare disorder that is 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.
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 (clinodactyly
), short fingers (brachydactyly
), and abnormal curvature of the spine (scoliosis
).
Many people with Silver-Russell syndrome have a small, triangular face
with distinctive features, including a prominent forehead
, a narrow chin
, a small jaw
, 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
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
Additional Information & Resources
Genetic Testing Information
- Genetic Testing Registry: Silver-Russell syndrome 1
- Genetic Testing Registry: Silver-russell syndrome 2
- Genetic Testing Registry: Silver-Russell syndrome 3
- Genetic Testing Registry: Silver-russell syndrome 4
- Genetic Testing Registry: Silver-Russell syndrome 5
- Genetic Testing Registry: Silver-Russell syndrome due to 11p15 microduplication
- Genetic Testing Registry: Silver-Russell syndrome due to 7p11.2p13 microduplication
- Genetic Testing Registry: Silver-Russell syndrome due to a point mutation
- Genetic Testing Registry: Silver-Russell syndrome due to an imprinting defect of 11p15
- Genetic Testing Registry: Silver-Russell syndrome due to maternal uniparental disomy of chromosome 11
- Genetic Testing Registry: Silver-Russell syndrome due to maternal uniparental disomy of chromosome 7
Genetic and Rare Diseases Information Center
Patient Support and Advocacy Resources
Clinical Trials
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
References
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- Binder G, Ziegler J, Schweizer R, Habhab W, Haack TB, Heinrich T, Eggermann T. Novel mutation points to a hot spot in CDKN1C causing Silver-Russell syndrome. Clin Epigenetics. 2020 Oct 19;12(1):152. doi: 10.1186/s13148-020-00945-y. Citation on PubMed
- Eggermann T, Spengler S, Gogiel M, Begemann M, Elbracht M. Epigenetic and genetic diagnosis of Silver-Russell syndrome. Expert Rev Mol Diagn. 2012 Jun;12(5):459-71. doi: 10.1586/erm.12.43. Citation on PubMed
- Eggermann T. Russell-Silver syndrome. Am J Med Genet C Semin Med Genet. 2010 Aug 15;154C(3):355-64. doi: 10.1002/ajmg.c.30274. Citation on PubMed
- 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. doi: 10.1038/ng1629. Epub 2005 Aug 7. Citation on PubMed
- Inoue T, Nakamura A, Iwahashi-Odano M, Tanase-Nakao K, Matsubara K, Nishioka J, Maruo Y, Hasegawa Y, Suzumura H, Sato S, Kobayashi Y, Murakami N, Nakabayashi K, Yamazawa K, Fuke T, Narumi S, Oka A, Ogata T, Fukami M, Kagami M. Contribution of gene mutations to Silver-Russell syndrome phenotype: multigene sequencing analysis in 92 etiology-unknown patients. Clin Epigenetics. 2020 Jun 16;12(1):86. doi: 10.1186/s13148-020-00865-x. Citation on PubMed
- Inoue T, Yagasaki H, Nishioka J, Nakamura A, Matsubara K, Narumi S, Nakabayashi K, Yamazawa K, Fuke T, Oka A, Ogata T, Fukami M, Kagami M. Molecular and clinical analyses of two patients with UPD(16)mat detected by screening 94 patients with Silver-Russell syndrome phenotype of unknown aetiology. J Med Genet. 2019 Jun;56(6):413-418. doi: 10.1136/jmedgenet-2018-105463. Epub 2018 Sep 21. Citation on PubMed
- Lokulo-Sodipe O, Ballard L, Child J, Inskip HM, Byrne CD, Ishida M, Moore GE, Wakeling EL, Fenwick A, Mackay DJG, Davies JH, Temple IK. Phenotype of genetically confirmed Silver-Russell syndrome beyond childhood. J Med Genet. 2020 Oct;57(10):683-691. doi: 10.1136/jmedgenet-2019-106561. Epub 2020 Feb 13. Citation on PubMed
- Lokulo-Sodipe O, Inskip HM, Byrne CD, Child J, Wakeling EL, Mackay DJG, Temple IK, Davies JH. Body Composition and Metabolism in Adults With Molecularly Confirmed Silver-Russell Syndrome. J Clin Endocrinol Metab. 2024 Oct 15;109(11):e2001-e2008. doi: 10.1210/clinem/dgae074. Citation on PubMed
- Saal HM, Harbison MD, Netchine I. Silver-Russell Syndrome. 2002 Nov 2 [updated 2025 Jan 9]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1324/ Citation on PubMed
- Wakeling EL, Brioude F, Lokulo-Sodipe O, O'Connell SM, Salem J, Bliek J, Canton AP, Chrzanowska KH, Davies JH, Dias RP, Dubern B, Elbracht M, Giabicani E, Grimberg A, Gronskov K, Hokken-Koelega AC, Jorge AA, Kagami M, Linglart A, Maghnie M, Mohnike K, Monk D, Moore GE, Murray PG, Ogata T, Petit IO, Russo S, Said E, Toumba M, Tumer Z, Binder G, Eggermann T, Harbison MD, Temple IK, Mackay DJ, Netchine I. Diagnosis and management of Silver-Russell syndrome: first international consensus statement. Nat Rev Endocrinol. 2017 Feb;13(2):105-124. doi: 10.1038/nrendo.2016.138. Epub 2016 Sep 2. Citation on PubMed
- Wakeling EL. Silver-Russell syndrome. Arch Dis Child. 2011 Dec;96(12):1156-61. doi: 10.1136/adc.2010.190165. Epub 2011 Feb 24. Citation on PubMed
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