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Genetics Home Reference: your guide to understanding genetic conditions
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Coffin-Siris syndrome

Reviewed May 2013

What is Coffin-Siris syndrome?

Coffin-Siris syndrome is a condition that affects several body systems. Although there are many variable signs and symptoms, hallmarks of this condition include developmental disability, abnormalities of the fifth (pinky) fingers or toes, and characteristic facial features.

Most affected individuals have mild to severe intellectual disability or delayed development of speech and motor skills such as sitting and walking. Another feature of Coffin-Siris syndrome is underdevelopment (hypoplasia) of the tips of the fingers or toes, or hypoplasia or absence of the nails. These abnormalities are most common on the fifth fingers or toes. In addition, most affected individuals have facial features described as coarse. These typically include a wide nose with a flat nasal bridge, a wide mouth with thick lips, and thick eyebrows and eyelashes. Affected individuals can have excess hair on other parts of the face and body (hirsutism), but scalp hair is often sparse. There is a range of facial features seen in people with Coffin-Siris syndrome, and not all affected individuals have the typical features. In addition, people with this condition may have an abnormally small head (microcephaly).

Additionally, some infants and children with Coffin-Siris syndrome have frequent respiratory infections, difficulty feeding, and an inability to gain weight at the expected rate (failure to thrive). Other signs and symptoms that may occur in people with this condition include short stature, low muscle tone (hypotonia), and abnormally loose (lax) joints. Abnormalities of the eyes, brain, heart, and kidneys may also be present.

How common is Coffin-Siris syndrome?

Coffin-Siris syndrome is a rare condition that is diagnosed in females more frequently than in males. Approximately 140 cases have been reported in the medical literature.

What genes are related to Coffin-Siris syndrome?

Coffin-Siris syndrome is caused by mutations in the ARID1A, ARID1B, SMARCA4, SMARCB1, or SMARCE1 gene. Each of these genes provides instructions for making one piece (subunit) of several different SWI/SNF protein complexes. SWI/SNF complexes regulate gene activity (expression) by a process known as chromatin remodeling. Chromatin is the network of DNA and protein that packages DNA into chromosomes. The structure of chromatin can be changed (remodeled) to alter how tightly regions of DNA are packaged. Chromatin remodeling is one way gene expression is regulated during development; when DNA is tightly packed, gene expression is often lower than when DNA is loosely packed.

Through their ability to regulate gene activity, SWI/SNF complexes are involved in many processes, including repairing damaged DNA; copying (replicating) DNA; and controlling the growth, division, and maturation (differentiation) of cells.

Although it is unclear what effect mutations in these genes have on SWI/SNF complexes, researchers suggest that the mutations result in abnormal chromatin remodeling. Disturbance of this process alters the activity of many genes and disrupts several cellular processes, which could explain the diverse signs and symptoms of Coffin-Siris syndrome.

Related Gene(s)

Changes in these genes are associated with Coffin-Siris syndrome.

  • ARID1A
  • ARID1B
  • SMARCA4
  • SMARCB1
  • SMARCE1

How do people inherit Coffin-Siris syndrome?

Coffin-Siris syndrome appears to follow an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. However, the condition is not usually inherited from an affected parent, but occurs from new (de novo) mutations in the gene that likely occur during early embryonic development.

Where can I find information about diagnosis or management of Coffin-Siris syndrome?

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

  • Gene Review: Coffin-Siris Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK131811/)
  • Genetic Testing Registry: Coffin-Siris syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0265338)

You might also find information on the diagnosis or management of Coffin-Siris syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/coffin-siris-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/coffin-siris-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 Coffin-Siris syndrome?

You may find the following resources about Coffin-Siris 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 Coffin-Siris syndrome?

  • dwarfism-onychodysplasia
  • fifth digit syndrome
  • mental retardation with hypoplastic fifth fingernails and toenails
  • short stature-onychodysplasia

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 Coffin-Siris syndrome?

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

What glossary definitions help with understanding Coffin-Siris syndrome?

autosomal ; autosomal dominant ; cell ; chromatin ; chromatin remodeling ; differentiation ; disability ; DNA ; dwarfism ; embryonic ; failure to thrive ; gene ; gene expression ; hirsutism ; hypoplasia ; hypotonia ; inheritance ; low muscle tone ; mental retardation ; microcephaly ; motor ; muscle tone ; pattern of inheritance ; protein ; respiratory ; short stature ; stature ; subunit ; syndrome

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

References

  • Euskirchen G, Auerbach RK, Snyder M. SWI/SNF chromatin-remodeling factors: multiscale analyses and diverse functions. J Biol Chem. 2012 Sep 7;287(37):30897-905. doi: 10.1074/jbc.R111.309302. Epub 2012 Sep 5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22952240?dopt=Abstract)
  • Gene Review: Coffin-Siris Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK131811/)
  • Santen GW, Aten E, Sun Y, Almomani R, Gilissen C, Nielsen M, Kant SG, Snoeck IN, Peeters EA, Hilhorst-Hofstee Y, Wessels MW, den Hollander NS, Ruivenkamp CA, van Ommen GJ, Breuning MH, den Dunnen JT, van Haeringen A, Kriek M. Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome. Nat Genet. 2012 Mar 18;44(4):379-80. doi: 10.1038/ng.2217. (http://www.ncbi.nlm.nih.gov/pubmed/22426309?dopt=Abstract)
  • Santen GW, Aten E, Vulto-van Silfhout AT, Pottinger C, van Bon BW, van Minderhout IJ, Snowdowne R, van der Lans CA, Boogaard M, Linssen MM, Vijfhuizen L, van der Wielen MJ, Vollebregt MJ; Coffin-Siris consortium, Breuning MH, Kriek M, van Haeringen A, den Dunnen JT, Hoischen A, Clayton-Smith J, de Vries BB, Hennekam RC, van Belzen MJ. Coffin-Siris syndrome and the BAF complex: genotype-phenotype study in 63 patients. Hum Mutat. 2013 Nov;34(11):1519-28. doi: 10.1002/humu.22394. Epub 2013 Aug 30. (http://www.ncbi.nlm.nih.gov/pubmed/23929686?dopt=Abstract)
  • Santen GW, Kriek M, van Attikum H. SWI/SNF complex in disorder: SWItching from malignancies to intellectual disability. Epigenetics. 2012 Nov;7(11):1219-24. doi: 10.4161/epi.22299. Epub 2012 Sep 25. Review. (http://www.ncbi.nlm.nih.gov/pubmed/23010866?dopt=Abstract)
  • Schrier SA, Bodurtha JN, Burton B, Chudley AE, Chiong MA, D'avanzo MG, Lynch SA, Musio A, Nyazov DM, Sanchez-Lara PA, Shalev SA, Deardorff MA. The Coffin-Siris syndrome: a proposed diagnostic approach and assessment of 15 overlapping cases. Am J Med Genet A. 2012 Aug;158A(8):1865-76. doi: 10.1002/ajmg.a.35415. Epub 2012 Jun 18. (http://www.ncbi.nlm.nih.gov/pubmed/22711679?dopt=Abstract)
  • Tsurusaki Y, Okamoto N, Ohashi H, Kosho T, Imai Y, Hibi-Ko Y, Kaname T, Naritomi K, Kawame H, Wakui K, Fukushima Y, Homma T, Kato M, Hiraki Y, Yamagata T, Yano S, Mizuno S, Sakazume S, Ishii T, Nagai T, Shiina M, Ogata K, Ohta T, Niikawa N, Miyatake S, Okada I, Mizuguchi T, Doi H, Saitsu H, Miyake N, Matsumoto N. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome. Nat Genet. 2012 Mar 18;44(4):376-8. doi: 10.1038/ng.2219. (http://www.ncbi.nlm.nih.gov/pubmed/22426308?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: May 2013
Published: July 7, 2014