Saethre- Chotzen Syndrome
Saether-Chotzen syndrome is a rare type of craniosynostosis- the early closing of one or more of the soft, fibrous seams(sutures) between the skull bone. When a suture closes too early, a baby skull cannot grow correctly.
Saethre-Chotzen syndrome is a genetic condition characterized by the premature fusion of certain skull bones. 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, 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 from 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.
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.
Causes:
Most cases of Saethre-Chotzen syndrome are 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 to a specific region 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 underline 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 intellectual disability, developmental delay, and learning difficulties.
Signs and Symptoms:
SCS presents in a variable fashion. The majority of individuals with SCS are moderately affected, with uneven facial features and a relatively flat face due to underdeveloped eye sockets, cheekbones, and lower jaw. In addition to the physical abnormality, people with SCS also experience growth delays, which results in relatively short stature. Although most individuals with SCS are of normal intelligence, some Individuals may have mild to moderate mental delays. More Severe Cases of SCS, with more serious facial deformities, occur when multiple cranial sutures close prematurely.
Cranial defects:
- Flat, asymmetric head and face
- Head is typically cone-shaped (acrocephaly) or flat (brachycephaly) but can also be long and narrow (Dolichocephaly).
- Head is short from front to back
- Lopsided face
- Low set hairline causing the forehead to appear tall and wide
Defects of the hands and feet:
- Webbing between the second and third finger and between the second and third toes
- Short fingers and toes
- Broad thumb and or a broad hallux with a valgus deformity.
- Hands have a single palmar flexion crease
Ocular defects:
- Unevenly positioned eyes that may be crossed(strabismus) or wide-set(hypertelorism)
- Vision problems due to abnormal facial anatomy, which causes mechanical disturbances of the extraocular muscles, resulting in strabismus(crossed eyes)
- Tear duct stenosis(narrowing of the tear duct)
- Drooping eyelids
- Downward slanting palpebral fissures(separation between upper and lower eyelids)
- Nearsightedness
- Epicanthal folds (skin folds of the upper eyelid covering the inner corner of the eye)
- Blepharophimosis(bilateral ptosis with reduced size of the eye)
- Optic atrophy
- Refractory errors
Ear, Nose, and mouth defects:
-Small, low-set ears that may be rotated somewhat backward and has a prominent(bulging) pinna.
- Beaked nose(slightly bent downward at the tip) that is slightly off-center and contains a deviated septum
- Malocclusion is associated with dental abnormalities including enamel hypoplasia(thin enamel due to incomplete formation), Hyperdontia (extra teeth), and peg teeth(small, abnormality shaped teeth)
- Cleft palate with a high arch
Less common defects:
- Short stature
- Vertebral fusion
- Congenital heart problems
- Speech problems
- Anal atresia (malformed rectum)
- Undescended testes (cryptorchidism)
- Renal kidney abnormality
- Personality disorders
Inheritance:
Saethre-Chptzen 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. In some cases, an affected person inherited the mutation from one affected parent. Other cases may result from new mutations in the end. These cases occur in people with no history of the disorder in their families. Each child of an individual with Sarthre- Chotzen syndrome has a 50% chance of inheriting the mutation.
Diagnosis:
Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at t 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:
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 genetic professional.
