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Saethre-Chotzen syndrome

Other Names for this Disease
  • Acrocephalo-syndactyly, type 3
  • Acrocephaly, skull asymmetry, and mild syndactyly
  • ACS 3
  • ACS3
  • Chotzen syndrome
More Names
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Your Question

I have have two sons affected by Saethre-Chotzen syndrome. One is mildly affected while the other has severe symptoms. Is my mildly-affected son at risk to have a child with severe symptoms similar to those seen in his brother?

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

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. The signs and symptoms of Saethre-Chotzen syndrome vary widely, even among affected individuals in the same family. Mutations in the TWIST1 gene cause Saethre-Chotzen syndrome. This condition is inherited in an autosomal dominant pattern. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene.[1]
Last updated: 4/22/2009

What causes Saethre-Chotzen syndrome?

Saethre-Chotzen syndrome is caused by mutations in the TWIST1 gene. 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.[1]

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.[1]

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 intellectual disability, developmental delay, and learning difficulties.[1]

Last updated: 4/21/2009

Is Saethre-Chotzen syndrome inherited?

Saethre-Chotzen syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.[1][2] 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.[1] 

Each child of an individual with Saethre-Chotzen syndrome has a 50% chance of inheriting the mutation.[2]
Last updated: 4/21/2009

Can an individual with mild symptoms of Saethre-Chotzen syndrome have a child with more severe symptoms of the condition?

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.[1]

Individuals who are known to have mutations in the TWIST1 may benefit from dicussing their risks of passing on the mutation to their offspring with a genetics professional.

Last updated: 4/21/2009

How can I find a genetics professional in my area?

Genetics clinics are a source of information for individuals and families regarding genetic conditions, treatment, inheritance, and genetic risks to other family members. More information about genetic consultations is available from Genetics Home Reference. To find a genetics clinic, we recommend that you contact your primary healthcare provider for a referral.

The following online resources can help you find a genetics professional in your community:

Last updated: 6/22/2012