Saethre-Chotzen syndrome

Version	Summary	Created by	Modification	Content Size	Created at	Operation
1		Nora Tang	+ 661 word(s)	661	2020-12-15 07:37:40

This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/saethre-chotzen-syndrome

Saethre-Chotzen syndrome is a genetic condition characterized by the premature fusion of certain skull bones (craniosynostosis).

genetic conditions

1. Introduction

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, rounded ears.

The signs and symptoms of Saethre-Chotzen syndrome vary widely, even among affected individuals in the same family. This condition can cause mild changes in the hands and feet, such as partial fusion of the skin between the second and third fingers on each hand and a broad or duplicated first (big) 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 variant of Saethre-Chotzen syndrome.

2. Frequency

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

3. Causes

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.

In a small number of people with Saethre-Chotzen syndrome, the condition is caused by 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 intellectual disability, 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.

4. Inheritance

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.

5. Other Names for This Condition

acrocephalosyndactyly III
acrocephalosyndactyly, type III
acrocephaly, skull asymmetry, and mild syndactyly
ACS III
ACS3
Chotzen syndrome
dysostosis craniofacialis with hypertelorism
SCS

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. HumGenet. 2003 Dec;114(1):68-76.
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 ofRobinow-Sorauf syndrome. Clin Genet. 2003 Jul;64(1):79-82.
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 theSaethre-Chotzen phenotype. Am J Med Genet. 2002 Jun 15;110(2):136-43.
Cunningham ML, Seto ML, Ratisoontorn C, Heike CL, Hing AV. Syndromiccraniosynostosis: from history to hydrogen bonds. Orthod Craniofac Res. 2007May;10(2):67-81. Review.
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 patientswith Saethre-Chotzen syndrome. Plast Reconstr Surg. 2005 Jun;115(7):1894-902;discussion 1903-5.
Gallagher ER, Ratisoontorn C, Cunningham ML. Saethre-Chotzen Syndrome. 2003May 16 [updated 2019 Jan 24]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE,Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK1189/
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.
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, CollmannH. Saethre-Chotzen syndrome caused by TWIST 1 gene mutations: functionaldifferentiation from Muenke coronal synostosis syndrome. Eur J Hum Genet. 2006Jan;14(1):39-48.

©Text is available under the terms and conditions of the Creative Commons-Attribution ShareAlike (CC BY-SA) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.

Upload a video for this entry

Information

Subjects: Genetics & Heredity

Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :

Nora Tang

View Times: 392

Entry Collection: MedlinePlus

Update Date: 24 Dec 2020

Table of Contents

Video Upload Options

Confirm

1. Introduction

2. Frequency

3. Causes

4. Inheritance

5. Other Names for This Condition

References

Video Upload Options

Confirm

1. Introduction

2. Frequency

3. Causes

3.1. The Gene and Chromosome Associated with Saethre-Chotzen Syndrome

4. Inheritance

5. Other Names for This Condition

References