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Saethre-Chotzen syndrome

Reviewed February 2008

What is Saethre-Chotzen syndrome?

Saethre-Chotzen syndrome is a genetic condition characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face.

Most people with Saethre-Chotzen syndrome have prematurely fused skull bones along the coronal suture, the growth line that goes over the head from ear to ear. Other parts of the skull may be malformed as well. These changes can result in an abnormally shaped head, a high forehead, a low frontal hairline, droopy eyelids (ptosis), widely spaced eyes, and a broad nasal bridge. One side of the face may appear noticeably different from the other (facial asymmetry). Most people with Saethre-Chotzen syndrome also have small, unusually shaped ears.

The signs and symptoms of Saethre-Chotzen syndrome vary widely, even among affected individuals in the same family. This condition can cause mild abnormalities of the hands and feet, such as fusion of the skin between the second and third fingers on each hand and a broad or duplicated great toe. Delayed development and learning difficulties have been reported, although most people with this condition are of normal intelligence. Less common signs and symptoms of Saethre-Chotzen syndrome include short stature, abnormalities of the bones of the spine (the vertebra), hearing loss, and heart defects.

Robinow-Sorauf syndrome is a condition with features similar to those of Saethre-Chotzen syndrome, including craniosynostosis and broad or duplicated great toes. It was once considered a separate disorder, but was found to result from mutations in the same gene and is now thought to be a mild variant of Saethre-Chotzen syndrome.

How common is Saethre-Chotzen syndrome?

Saethre-Chotzen syndrome has an estimated prevalence of 1 in 25,000 to 50,000 people.

What are the genetic changes related to Saethre-Chotzen syndrome?

Mutations in the TWIST1 gene cause Saethre-Chotzen syndrome. The TWIST1 gene provides instructions for making a protein that plays an important role in early development. This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. The TWIST1 protein is active in cells that give rise to bones, muscles, and other tissues in the head and face. It is also involved in the development of the limbs.

Mutations in the TWIST1 gene prevent one copy of the gene in each cell from making any functional protein. A shortage of the TWIST1 protein affects the development and maturation of cells in the skull, face, and limbs. These abnormalities underlie the signs and symptoms of Saethre-Chotzen syndrome, including the premature fusion of certain skull bones.

A small number of cases of Saethre-Chotzen syndrome have resulted from a structural chromosomal abnormality, such as a deletion or rearrangement of genetic material, in the region of chromosome 7 that contains the TWIST1 gene. When Saethre-Chotzen syndrome is caused by a chromosomal deletion instead of a mutation within the TWIST1 gene, affected children are much more likely to have mental retardation, developmental delay, and learning difficulties. These features are typically not seen in classic cases of Saethre-Chotzen syndrome. Researchers believe that a loss of other genes on chromosome 7 may be responsible for these additional features.

Can Saethre-Chotzen syndrome be inherited?

This 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. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family.

Some people with a TWIST1 mutation do not have any of the obvious features of Saethre-Chotzen syndrome. These people are still at risk of passing on the gene mutation, and may have a child with craniosynostosis and the other typical signs and symptoms of the condition.

Where can I find information about treatment for Saethre-Chotzen syndrome?

You may find information on treatment or management of Saethre-Chotzen syndrome or some of its symptoms in the links below, particularly the links for Gene Reviews, MedlinePlus Encyclopedia, Educational resources, and Patient support.

Where can I find additional information about Saethre-Chotzen syndrome?

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

  • MedlinePlus - Health information
    • Encyclopedia: Craniosynostosis (http://www.nlm.nih.gov/medlineplus/ency/article/001590.htm)
    • Encyclopedia: Skull of a Newborn (image) (http://www.nlm.nih.gov/medlineplus/ency/imagepages/1127.htm)
    • Health Topic: Facial Injuries and Disorders (http://www.nlm.nih.gov/medlineplus/facialinjuriesanddisorders.html)
    • Health Topic: Head and Brain Malformations (http://www.nlm.nih.gov/medlineplus/headandbrainmalformations.html)
  • Additional NIH Resources - National Institutes of Health
    National Institute of Neurological Disorders and Stroke: Craniosynostosis Information Page (http://www.ninds.nih.gov/disorders/craniosynostosis/craniosynostosis.htm)
  • Educational resources - Information pages
    • Children's Hospital Boston (http://www.childrenshospital.org/az/Site1537/mainpageS1537P0.html)
    • Cincinnati Children's Hospital Medical Center: Craniosynostosis (http://www.cincinnatichildrens.org/health/info/craniofacial/diagnose/)
    • Johns Hopkins Collaboration for Craniofacial Development and Disorders (http://www.hopkinsmedicine.org/craniofacial/Education/DefinedArticle.cfm?MUArticleID=68&Source=Family)
    • Madisons Foundation (http://www.madisonsfoundation.org/index.php/component/option,com_mpower/diseaseID,527/)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=794)
    • Seattle Children's Hospital and Regional Medical Center (http://craniofacial.seattlechildrens.org/conditions_treated/saethre.asp)
  • Patient support - For patients and families
    • AboutFace USA (http://www.aboutfaceusa.org/)
    • Children's Craniofacial Association (http://www.ccakids.com/)
    • Family Village (http://www.familyvillage.wisc.edu/lib_cran.htm)
    • Let's Face It (http://www.dent.umich.edu/faceit/)
    • National Organization for Rare Disorders (http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Saethre+Chotzen+Syndrome)
    • Resource list from the University of Kansas Medical Center (http://www.kumc.edu/gec/support/craniofa.html)

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

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=scs)
  • Gene Tests - DNA tests ordered by healthcare professionals (http://www.genetests.org/query?testid=2030)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/search/condition=%22Saethre-Chotzen+syndrome%22+OR+%22Acrocephalosyndactylia%22+OR+%22Saethre-Chotzen+Syndrome%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=(Acrocephalosyndactylia[MAJR])+AND+((saethre-chotzen+syndrome[TIAB])+OR+(acs+iii[TIAB])+OR+(acs3[TIAB])+OR+(dysostosis+craniofacialis+with+hypertelorism[TIAB])+OR+(chotzen+syndrome[TIAB]))+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=3600+Days)
  • OMIM - Genetic disorder catalog
    • OMIM topic: Robinow-Sorauf syndrome (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=180750)
    • OMIM topic: Saethre-Chotzen syndrome (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=101400)

What other names do people use for Saethre-Chotzen syndrome?

  • acrocephalosyndactyly III
  • Acrocephalosyndactyly, type III
  • Acrocephaly, Skull Asymmetry, and Mild Syndactyly
  • ACS3
  • ACS III
  • Chotzen syndrome
  • dysostosis craniofacialis with hypertelorism
  • SCS

See 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 Saethre-Chotzen syndrome?

  • See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.
  • Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).
  • Submit your question to Ask the Geneticist (http://www.askthegen.org/).

What glossary definitions help with understanding Saethre-Chotzen syndrome?

autosomal ; autosomal dominant ; brachycephaly ; cell ; chromosome ; coronal ; coronal suture ; craniosynostosis ; deletion ; developmental delay ; DNA ; gene ; great toe ; hypertelorism ; mental retardation ; mutation ; new mutation ; prevalence ; protein ; ptosis ; rearrangement ; short stature ; sign ; stature ; symptom ; syndactyly ; syndrome ; tissue ; transcription ; transcription factor ; vertebra

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

References
  • Cai J, Goodman BK, Patel AS, Mulliken JB, Van Maldergem L, Hoganson GE, Paznekas WA, Ben-Neriah Z, Sheffer R, Cunningham ML, Daentl DL, Jabs EW. Increased risk for developmental delay in Saethre-Chotzen syndrome is associated with TWIST deletions: an improved strategy for TWIST mutation screening. Hum Genet. 2003 Dec;114(1):68-76. Epub 2003 Sep 25. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=14513358)
  • Cai J, Shoo BA, Sorauf T, Jabs EW. A novel mutation in the TWIST gene, implicated in Saethre-Chotzen syndrome, is found in the original case of Robinow-Sorauf syndrome. Clin Genet. 2003 Jul;64(1):79-82. No abstract available. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12791045)
  • Chun K, Teebi AS, Jung JH, Kennedy S, Laframboise R, Meschino WS, Nakabayashi K, Scherer SW, Ray PN, Teshima I. Genetic analysis of patients with the Saethre-Chotzen phenotype. Am J Med Genet. 2002 Jun 15;110(2):136-43. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=12116251)
  • Cunningham ML, Seto ML, Ratisoontorn C, Heike CL, Hing AV. Syndromic craniosynostosis: from history to hydrogen bonds. Orthod Craniofac Res. 2007 May;10(2):67-81. Review. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=17552943)
  • de Heer IM, de Klein A, van den Ouweland AM, Vermeij-Keers C, Wouters CH, Vaandrager JM, Hovius SE, Hoogeboom JM. Clinical and genetic analysis of patients with Saethre-Chotzen syndrome. Plast Reconstr Surg. 2005 Jun;115(7):1894-902; discussion 1903-5. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=15923834)
  • Gene Review: Saethre-Chotzen Syndrome (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=scs)
  • Gripp KW, Zackai EH, Stolle CA. Mutations in the human TWIST gene. Hum Mutat. 2000;15(2):150-5. Review. Erratum in: Hum Mutat 2000;15(5):479. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=10649491)
  • Kress W, Schropp C, Lieb G, Petersen B, Büsse-Ratzka M, Kunz J, Reinhart E, Schäfer WD, Sold J, Hoppe F, Pahnke J, Trusen A, Sörensen N, Krauss J, Collmann H. Saethre-Chotzen syndrome caused by TWIST 1 gene mutations: functional differentiation from Muenke coronal synostosis syndrome. Eur J Hum Genet. 2006 Jan;14(1):39-48. (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&dopt=Abstract&list_uids=16251895)

 

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: February 2008
Published: January 12, 2009