Saethre Chotzen Syndrome

National Organization for Rare Disorders, Inc.

Skip to the navigation


It is possible that the main title of the report Saethre Chotzen Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


  • ACS3
  • SCS
  • acrocephalosyndactyly type III
  • acrocephaly, skull asymmetry, and mild syndactyly
  • ACS type III
  • Chotzen syndrome

Disorder Subdivisions

  • None

General Discussion

Saethre Chotzen syndrome (SCS) belongs to a group of rare genetic disorders known as "acrocephalosyndactyly" disorders. All of these are characterized by premature closure of the fibrous joints (cranial sutures) between certain bones of the skull (craniosynostosis), and/or webbing or fusion (syndactyly) of certain fingers or toes (digits).

In many infants with SCS, cranial sutures may fuse unevenly and this may contribute to the head and face appearing to be dissimilar from one side to the other (craniofacial asymmetry). Additional variations of the skull and facial (craniofacial) region may also be present, such as widely spaced eyes (ocular hypertelorism) with unusually shallow eye cavities (orbits); drooping of the upper eyelids (ptosis); and a state where the eyes do not point in the same direction (strabismus). Some affected individuals may also have a "beaked" nose; deviation of the partition that separates the nostrils (deviated nasal septum); small, low-set ears; and an underdeveloped upper jaw (hypoplastic maxilla). The disorder is also associated with variations of the hands and feet, such as partial fusion of soft tissues (cutaneous syndactyly) of certain fingers and toes (digits); unusually short digits (brachydactyly); and broad great toes. Intelligence is usually normal. SCS is inherited in an autosomal dominant manner.


SCS is primarily characterized by premature closure of the fibrous joints (cranial sutures) between certain bones in the skull (craniosynostosis), distinctive facial variations, and/or variations of the fingers and toes (digits). However, associated symptoms and findings may be extremely variable, including among affected members of the same family. For example, there have been reports in which some family members have had characteristic digital abnormalities alone, whereas others have been primarily affected by craniosynostosis.

When craniosynostosis is present, the degree of skull (cranial) malformation may be variable, depending on the specific cranial sutures involved and the order and rate of progression. In many affected infants and children, early closure of the coronal suture which is found between bones forming the forehead (frontal bone) and the upper sides of the skull causes the top of the head to appear pointed (acrocephaly) or the head to seem unusually short or broad (brachycephaly). In addition, the cranial sutures often fuse unevenly, causing the head and face to appear somewhat dissimilar from one side to the other (plagiocephaly and facial asymmetry). Cases have also been reported in which the head appears triangular in shape (trigonocephaly) or the forehead is unusually prominent due to premature closure of the suture of the frontal bone (i.e. frontal or metopic suture). In some instances, early closure of certain cranial sutures may lead to abnormally increased pressure within the skull (intracranial pressure).

Many individuals with SCS have additional craniofacial variations, resulting in a subtle, but distinctive, facial appearance. Such abnormalities may include a broad forehead with a low hairline; drooping of the upper eyelids (ptosis); a "beaked" nose, depressed nasal bridge, and deviated nasal septum; unusually broad, flat mid-facial regions (midface hypoplasia); and a small upper jaw (hypoplastic maxilla), with protrusion of the lower jaw (relative mandibular prognathism). Additional eye (ocular) abnormalities are also often present, such as widely spaced eyes (ocular hypertelorism); shallow eye cavities (orbits); strabismus; and/or abnormal narrowing of the tear ducts (lacrimal duct stenosis), potentially causing decreased tearing and an increased susceptibility to eye infections.

Other craniofacial variations may also be associated with the disorder. Many affected individuals have small, low-set, or differences in parts of the ear (e.g. prominent ear crura). In addition, mild hearing impairment is frequent. Abnormalities of the mouth (oral) region often include a highly arched roof of the mouth (palate) and dental defects, such as absence or malformation of certain teeth, the presence of extra (supernumerary) teeth, and/or improper contact of the teeth of the upper jaw with those of the lower jaw (malocclusion) may occur. In rare cases, there may be incomplete closure of the roof of the mouth (cleft palate).

SCS may also be characterized by variations of the fingers and toes (digits). Some affected individuals have partial webbing or fusion of the soft tissues (cutaneous syndactyly) of certain digits, particularly between the second and third fingers and second and third toes. However, less commonly, syndactyly extends from the second to the fourth fingers or involves other toes. Additional digital malformations may include unusually short fingers and toes (brachydactyly); abnormal bending or deviation (clinodactyly) of the fifth fingers ("pinkies"); "finger-like" thumbs; and/or broad, deviating great toes.

Additional physical abnormalities may also be associated with SCS. Some affected individuals have short stature. Less commonly, musculoskeletal abnormalities may also be present, such as union or fusion of certain bones of the spinal column within the neck (cervical vertebrae), abnormal fusion of the forearm bones (radioulnar synostosis), limited extension of the elbows or knees, short collarbones (clavicles), and/or hip deformities (coxa valga). Occasional additional findings may include failure of the testes to descend into the scrotum (cryptorchidism) in affected males; kidney (renal) abnormalities; and/or heart (cardiac) defects.

Most individuals with SCS have normal intelligence. However, mild to moderate intellectual disability is sometimes present.

For further information, please see the "Causes" section of this report below regarding the "TWIST1" gene.


In most individuals, SCS is caused by mutations in the TWIST1 gene. The TWIST1 gene has been mapped to the short arm (p) of chromosome 7 (7p21). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as "p" and a long arm identified by the letter "q." Chromosomes are further subdivided into bands that are numbered. For example, "7p21" refers to band 21 on the short arm of chromosome 7.

Although learning differences may be noted in individuals with mutations in TWIST1, severe delay or intellectual disability is not typical. In contrast, individuals with a deletion (missing piece) of chromosome 7p21, that includes TWIST1 and other adjacent genes, usually show significant intellectual disability. In most cases, individuals with a SCS associated mutation will manifest some features of this condition (high penetrance). However, they type and severity of manifestations may vary greatly between individuals (variable expressivity).

SCS is an autosomal dominant condition. Dominant genetic disorders occur when only a single copy of an abnormal gene is sufficient to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% (1 in2) for each pregnancy. The risk is the same for males and females.

Affected Populations

SCS affects males and females in equal numbers. Due to its variability including that manifestations can be mild, SCS may often go unrecognized. Therefore, it is difficult to determine the true frequency of the disorder in the general population.

Standard Therapies


The diagnosis of SCS is primarily based on physical signs and symptoms. Molecular genetic testing for mutations in the TWIST1 gene can be identified in some, but not all, individuals.


The management of SCS is directed toward identifying potentially medically important manifestations in an individual and treating those manifestations. Such treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians; surgeons; physicians who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues (orthopedists); physicians who specialize in disorders of the ears, nose, and throat (otolaryngologists); physicians who diagnose and treat neurological disorders (neurologists); and/or other health care professionals.

Surgery may be advised in the first year of life to help prevent or correct early closure of cranial sutures, to prevent increased intracranial pressure, and to prevent progressive facial asymmetry. Corrective and reconstructive surgery may also be performed to help correct certain craniofacial malformations and associated findings, syndactyly, other skeletal defects, or other physical abnormalities potentially associated with the disorder. The surgical procedures performed will depend upon the severity and location of the anatomical abnormalities, their associated symptoms, and other factors.

Evaluation by an ophthalmologist for eye and vision abnormalities and audiologic evaluation for hearing loss is recommended. X-ray of the neck bones should be considered at around age 2 years. Other tests may be considered depending on an individual's findings.

If intellectual disability is identified, early intervention may be important to ensure that children with SCS reach their potential. Special services that may be beneficial include special education and/or other medical, social, or vocational services.

Genetic counseling will be of benefit for affected individuals and their families. If mutation is not identified, an evaluation to assess for features of SCS should be considered for the relevant family members.

Investigational Therapies

Information on current clinical trials is posted on the Internet at All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010


For information about clinical trials sponsored by private sources, contact:



Jones KL. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W.B. Saunders Company; 1997:412-421, 428-429.

Buyse ML. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications, Inc.; 1990:36-40, 154, 460-461, 467-468.

Gorlin RJ, et al, eds. Syndromes of the Head and Neck. 3rd ed. New York, NY: Oxford University Press; 1990:520-534.


El Ghouzzi V, Legeai-Mallet L, Aresta S, et al. Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location. Hum Mol Genet. 2000;9:813-819.

Gripp KW, Zackai EH, Stolle CA. Mutations in the human TWIST gene. Hum Mutat. 2000;15(5):479.

El Ghouzzi V, Lajeunie E, Le Merrer M, et al. Mutations within or upstream of the basic helix-loop-helix domain of the TWIST gene are specific to Saethre-Chotzen syndrome. Europ J Hum Genet. 1999;7(1):27-33.

Johnson D, Horsley SW, Moloney DM, et al. A comprehensive screen for TWIST mutations in patients with craniosynostosis identifies a new microdeletion syndrome of chromosome band 7p21.1. Am J Hum Genet. 1998;63(5):1282-1293.

Paznekas WA, Cunningham ML, Howard TD, et al. Genetic heterogeneity of Saethre-Chotzen syndrome, due to TWIST and FGFR mutations. Am J Hum Genet. 1998;62(6):1370-1380.

Howard TD, Paznekas WA, Green ED, et al. Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome. Nature Genet. 1997;15(1):36-41.

Pantke OA, Cohen MM Jr, Witkop CJ Jr, et al. The Saethre-Chotzen syndrome. Birth Defects Orig Artic Ser. 1975;11(2):190-225.


Emily R, Gallagher ER, Ratisoontorn C, Cunningham ML. (Updated June 14, 2012). Saethre-Chotzen Syndrome. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2012. Available at Accessed July 3, 2012.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Saethre-Chotzen Syndrome;SCS. Entry No: 101400. Last Edited February 11, 2008. Available at: Accessed July 3, 2012.


Children's Craniofacial Association

13140 Coit Road

Suite 517

Dallas, TX 75240


Tel: (214)570-9099

Fax: (214)570-8811

Tel: (800)535-3643



March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763


FACES: The National Craniofacial Association

PO Box 11082

Chattanooga, TN 37401

Tel: (423)266-1632

Fax: (423)267-3124

Tel: (800)332-2373



The Arc

1825 K Street NW, Suite 1200

Washington, DC 20006

Tel: (202)534-3700

Fax: (202)534-3731

Tel: (800)433-5255

TDD: (817)277-0553



Let's Face It

University of Michigan, School of Dentistry / Dentistry Library

1011 N. University

Ann Arbor, MI 48109-1078


Tel: (360)676-7325




PO Box 751112

Las Vegas, NV 89136


Tel: (702)769-9264

Fax: (702)341-5351

Tel: (888)486-1209




333 East 30th Street, Lobby Unit

New York, NY 10016

Tel: (212)263-6656

Fax: (212)263-7534



Headlines - Craniofacial Support Group

128 Beesmoor Road

Frampton Cotterell

Bristol, BS36 2JP

United Kingdom

Tel: 01454850557



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223


Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766



Cleft Lip and Palate Foundation of Smiles

2044 Michael Ave SW

Wyoming, MI 49509

Tel: (616)329-1335



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see