Rare Endocrinology News

Disease Profile

Saethre-Chotzen syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Antenatal

ICD-10

Q87.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Acrocephalo-syndactyly, type 3; ACS3; Chotzen syndrome;

Categories

Congenital and Genetic Diseases; Eye diseases; Musculoskeletal Diseases;

Summary

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 and symmetry of the head and face. Other features may include webbing of certain fingers or toes (syndactyly), small or unusually shaped ears, short stature, and abnormalities of the bones in the spine (the vertebrae). The signs and symptoms of Saethre-Chotzen syndrome vary widely, even among affected individuals in the same family. Mutations (variants) in the TWIST1 gene cause most cases of Saethre-Chotzen syndrome. The 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][2] Treatment is aimed at addressing the symptoms found in each individual and may require the coordinated efforts of a team of specialists. Surgery is often needed to prevent or correct early closure of the cranial sutures and correct certain craniofacial abnormalities, syndactyly and/or skeletal defects.[2]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Craniosynostosis
0001363
Facial asymmetry
Asymmetry of face
Crooked face
Unsymmetrical face

[ more ]

0000324
Finger syndactyly
0006101
High forehead
0000348
30%-79% of people have these symptoms
Abnormality of the antihelix
0009738
Bilateral single transverse palmar creases
0007598
Blepharospasm
Eyelid spasm
Eyelid twitching
Involuntary closure of eyelid
Spontaneous closure of eyelid

[ more ]

0000643
Brachycephaly
Short and broad skull
0000248
Brachydactyly
Short fingers or toes
0001156
Convex nasal ridge
Beaked nose
Beaklike protrusion
Hooked nose
Polly beak nasal deformity

[ more ]

0000444
Delayed cranial suture closure
0000270
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
External ear malformation
0008572
Hyperlordosis
Prominent swayback
0003307
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Low anterior hairline
Low frontal hairline
Low-set frontal hairline

[ more ]

0000294
Microtia
Small ears
Underdeveloped ears

[ more ]

0008551
Narrow internal auditory canal
0011386
Narrow palate
Narrow roof of mouth
0000189
Open bite
Absence of overlap of upper and lower teeth
Open bite between upper and lower teeth

[ more ]

0010807
Plagiocephaly
Flat head syndrome
Flattening of skull
Rhomboid shaped skull

[ more ]

0001357
Prominent crus of helix
0009899
Prominent nasal bridge
Elevated nasal bridge
High nasal bridge
Prominent bridge of nose
Prominent nasal root
Protruding bridge of nose
Protruding nasal bridge

[ more ]

0000426
Ptosis
Drooping upper eyelid
0000508
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
5%-29% of people have these symptoms
Abnormal form of the vertebral bodies
0003312
Abnormality of cardiovascular system morphology
0030680
Amblyopia
Lazy eye
Wandering eye

[ more ]

0000646
Broad thumb
Broad thumbs
Wide/broad thumb

[ more ]

0011304
Cleft palate
Cleft roof of mouth
0000175
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

0000405
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Hallux valgus
Bunion
0001822
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion

[ more ]

0000327
Hypotelorism
Abnormally close eyes
Closely spaced eyes

[ more ]

0000601
Increased intracranial pressure
Rise in pressure inside skull
0002516
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Intellectual disability, moderate
IQ between 34 and 49
0002342
Low-set ears
Low set ears
Lowset ears

[ more ]

0000369
Migraine
Intermittent migraine headaches
Migraine headache
Migraine headaches

[ more ]

0002076
Optic atrophy
0000648
Proximal radio-ulnar synostosis
0005037
Scoliosis
0002650
Seizure
0001250
Sensorineural hearing impairment
0000407
Short stature
Decreased body height
Small stature

[ more ]

0004322
Sleep apnea
Pauses in breathing while sleeping
0010535
Triphalangeal thumb
Finger-like thumb
0001199
Percent of people who have these symptoms is not available through HPO
Abnormal heart morphology
Abnormality of the heart
Abnormally shaped heart
Heart defect

[ more ]

0001627
Abnormal nasolacrimal system morphology
0000614
Abnormality of pelvic girdle bone morphology
Abnormal shape of pelvic girdle bone
0002644
Absent first metatarsal
Absent 1st long bone of foot
0010104

Cause

Most cases of Saethre-Chotzen syndrome are caused by mutations (pathogenic variants) in the TWIST1 gene.[1][2] 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 (variants) 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 (7p21). 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][2][3]

At least one individual with Saethre-Chotzen syndrome has been described with a mutation (variant) in the FGFR2 gene.[2][4]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Saethre-Chotzen syndrome. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Saethre-Chotzen syndrome. Click on the link to view a sample search on this topic.

          References

          1. Saethre-Chotzen syndrome. Genetics Home Reference (GHR). February 2008; https://ghr.nlm.nih.gov/condition/saethre-chotzen-syndrome.
          2. Bayman G. Saethre Chotzen Syndrome. National Organization for Rare Disorders (NORD). 2015; https://rarediseases.org/rare-diseases/saethre-chotzen-syndrome/.
          3. Gallagher ER, Ratisoontorn C, Cunningham ML. Saethre-Chotzen Syndrome. GeneReviews. June 14, 2012; https://www.ncbi.nlm.nih.gov/books/NBK1189/.
          4. SAETHRE-CHOTZEN SYNDROME; SCS. Online Mendelian Inheritance in Man (OMIM). February 11, 2008; https://www.omim.org/entry/101400.

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