Saethre-Chotzen syndrome (SCS) is part of the disease of craniosynostosis group [1]. Patients usually have normal intelligence levels, despite the cranium malformation, due to prematurely fused coronal suture, but cases of delayed neuromotor development and learning difficulties have been reported. Women with SCS have increased breast cancer risk [2]. Clinical characteristics consist of a low frontal hairline, broad and prominent nasal bridge and convex nasal ridge, epicanthus, eyelid ptosis or blepharospasm, hypotelorism or hypertelorism, brachycephaly or plagiocephaly, high forehead and facial asymmetry. The shape of the ears may also be abnormal, with prominent crus of helix. Associated hands and feet malformations consist of bilateral single transverse palmar creases, syndactyly, broad thumbs, brachydactyly, hallux valgus, triphalangeal thumb, partial duplication of the distal phalanx of the second or third fingers, clinodactyly of the fifth finger, absent first metatarsal bone, proximal radio-ulnar synostosis or duplicated first toe. Supplementary skeleton anomalies consist of unusual vertebral shape, hyperlordosis or scoliosis and short stature. Patients sometimes have visceral malformations, like heart defects, cryptorchidism or sensorial organ malfunction, such as deafness. Viscerocranium malformations sometimes also include shallow orbits, narrow internal auditory canal and palate or cleft palate, open bite, maxillary hypoplasia, malar flattening, cleft chin and abnormality of the nasolacrimal system. There may be an ocular malfunction in SCS affected individuals, such as strabismus, amblyopia or optic atrophy, while the ears may be low set or present with antihelix anomalies or microtia. Patients sometime complain about migraine or have seizures, sleep apnea or signs of increased intracranial pressure.

This condition should be differentiated from Gorlin-Chaudhry-Moss syndrome [3] and Muenke syndrome [4], that may have similar clinical traits.

• Short Stature

  […] and some webbing of the fingers a broad or duplicated toe Less common symptoms include: short stature abnormalities in the bones of the spine hearing loss [3] heart defects Non-physical Symptoms Most patients with this condition have normal intelligence [pfond.cmmt.ubc.ca]

  Its phenotype includes uni– or bicoronal synostosis, short stature, facial dysmorphism and variable anomalies of the hands and feet. Due to its poor sonographic manifestation a prenatal diagnosis of SCS is challenging. [journals.viamedica.pl]

  Its phenotype includes uni- or bicoronal synostosis, short stature, facial dysmorphism and variable anomalies of the hands and feet. Due to its poor sonographic manifestation a prenatal diagnosis of SCS is challenging. [ncbi.nlm.nih.gov]

  In addition to fused sutures, children with Saethre Chotzen syndrome also have a characteristic low-set hairline, a “beaked” nose and short stature. [mercy.net]

• Short Finger

  Since the autosomal dominant Saethre-Chotzen syndrome may show similar cranio-facial features, short fingers with non-obligatory cutaneous syndactyly, and ossification defects of the cranial vault, the Saethre-Chotzen syndrome should also be considered [ncbi.nlm.nih.gov]

  […] wide head, one coronal suture affected: Plagiocephaly = an asymmetrical head); droopy eyelids (ptosis); short fingers, joining of the fingers (syndactyly) and broad toes (rarely cause any problems); and fusion of bones in the neck rarely causing problems [headlines.org.uk]

  Patients typically present with a low set hairline and short fingers and toes in addition to the skull deformities. Treatment plan: 4-6 months: Posterior Cranial vault Distraction 9-12 months: Anterior Cranial vault remodeling [ippcs.org]

• Short Stature in Children

  In addition to fused sutures, children with Saethre Chotzen syndrome also have a characteristic low-set hairline, a “beaked” nose and short stature. [mercy.net]

  In addition to fused coronal sutures, children with Saethre Chotzen syndrome also have a characteristic low-set hairline, a “beaked” nose and short stature. [med.unc.edu]

• Low Set Ears

  Clinical features of this syndrome include unilateral or bilateral coronal synostosis, ptosis, low-set ears, hearing loss, hypertelorism, maxillary hypoplasia, deviated nasal septum, broad great toes, clinodactyly, and syndactyly. [ncbi.nlm.nih.gov]

  The major signs of the syndrome are: fusion of certain head bones that sometimes causes the head and face to be asymmetrical; low hairline with upturned hair follicles; ptosis (droopy eyelids); low-set ears and minor irregularities at the top of the ear [facesofchildren.org]

  Some children with Saethre-Chotzen syndrome may have additional craniofacial anomalies such as cleft palate, low-set ears and dental issues. Children with Saethre-Chotzen syndrome also commonly have birth defects affecting the hands and feet. [chop.edu]

• Hearing Impairment

  The ears are often small and low-set with prominent crura and hearing impairment may occur. [accessanesthesiology.mhmedical.com]

  Complete Probemix List New and Improved Products IVD-Registered Products Bacteria Blood Cancers Cardiovascular Carrier Endocrine & Reproductive Gastrointestinal & Liver Hearing Impairment Hereditary Blood Disorders Immunological Imprinting Intellectual [mlpa.com]

  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 [rarediseases.info.nih.gov]

  In addition, mild hearing impairment is frequent. [rarediseases.org]

• Blepharoptosis

  To illustrate the phenotypic variability in SCS, we describe an unusual infant who presented for evaluation of cleft palate and blepharoptosis. [ncbi.nlm.nih.gov]

  Some of these patients underwent surgical correction of brachycephaly and blepharoptosis with good results. * Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, Chiba University, Chiba † Department of Neurosurgery, Fujikawa [journals.lww.com]

• Hypertelorism

  Clinical features of this syndrome include unilateral or bilateral coronal synostosis, ptosis, low-set ears, hearing loss, hypertelorism, maxillary hypoplasia, deviated nasal septum, broad great toes, clinodactyly, and syndactyly. [ncbi.nlm.nih.gov]

  Chotzen, German psychiatrist, 20th century an autosomal-dominant disorder characterized by acrocephalosyndactyly in which the syndactyly is mild and by hypertelorism, ptosis, and sometimes mental retardation. [medical-dictionary.thefreedictionary.com]

  The face is typically flat and often asymmetrical with a wide forehead, low frontal hairline, ptosis, hypertelorism, hypoplastic maxilla, deviated nasal septum, high-arched palate (or rarely cleft palate), and dental anomalies (eg, abnormal enamel with [accessanesthesiology.mhmedical.com]

• Beaked Nose

  The Saethre-Chotzen Syndrome (SCS) is characterized by craniosynostosis, low-set frontal hairline, parrot-beaked nose with deviated septum, ptosis of the eyelids, strabismus, refractive error, tear duct stenosis, dystopia canthorum, brachydactyly and [ncbi.nlm.nih.gov]

  In addition to fused sutures, children with Saethre Chotzen syndrome also have a characteristic low-set hairline, a “beaked” nose and short stature. [mercy.net]

  In addition to fused coronal sutures, children with Saethre Chotzen syndrome also have a characteristic low-set hairline, a “beaked” nose and short stature. [med.unc.edu]

  ’ nose and a septum (the partition between the nostrils) that is deviated, or crooked; and short fingers (a condition known as brachydactyly), with a partial fusion of the second and third fingers and/or toes. [facesofchildren.org]

• Broad Nasal Bridge

  Other symptions include: Head/Face: abnormally shaped head a high forehead a low frontal hair line facial asymmetry palatal anomalies [4] Eyes/Nose/Ears: droopy eyes (ptosis) widely spaced eyes broad nasal bridge small unusually shaped ears Other physical [pfond.cmmt.ubc.ca]

  Abnormally shaped head, eyes that are widely spaced, droopy eyelids, a broad nasal bridge, unusually shaped ears, poor facial asymmetry are all common characteristics of Saethre-Chotzen syndrome. Breathing and eating problems are possible. [grinerplasticsurgery.com]

  Other morphological characteristics of this syndrome are the following: Low frontal hairline Broad nasal bridge and possible deviated nasal septum (DNS) Droopy eyelids (ptosis) Widely spaced eyes Mild syndactylies ETIOLOGY The mutations in the gene Twist [craniofacial.org]

  Symptoms of Saethre-Chotzen syndrome include the following: Craniosynostosis, usually of the lambdoid or coronal sutures High forehead Low set hairline Droopy eyelids Widely spaced and bulging eyes Vision disturbances Broad nasal bridge Underdeveloped [dellchildrens.net]

• Nystagmus

  Hum Mol Genet 9:813–819 Article PubMed Google Scholar Faugere V, Tuffery-Giraud S, Hamel C, Claustres M (2003) Identification of three novel OA1 gene mutations identified in three families misdiagnosed with congenital nystagmus and carrier status determination [link.springer.com]

  Other observed ocular characteristics include astigmatism, amblyopia, myopia/hyperopia, monocular elevation deficit, rotary nystagmus, extraocular muscle agenesis, and lower lid entropion.[10] Finally, one significant consideration in patients with SCS [eyewiki.aao.org]

• Rotary Nystagmus

  Other observed ocular characteristics include astigmatism, amblyopia, myopia/hyperopia, monocular elevation deficit, rotary nystagmus, extraocular muscle agenesis, and lower lid entropion.[10] Finally, one significant consideration in patients with SCS [eyewiki.aao.org]

• Vertigo

  […] and cataracts and some forms of cancer and other diseases; severe exposure can cause death within hours; "he was suffering from radiation" Ramsay Hunt syndrome - syndrome resulting from infection by the herpes varicella zoster virus; characterized by vertigo [thefreedictionary.com]

Saethre-Chotzen syndrome diagnosis is primarily clinical, but certainty is added by genetic testing. If typical traits are absent, one study [5] concluded that ptosis, facial asymmetry and low frontal hairline are good indicators. The disease is caused by mutations in the TWIST1 gene and is inherited or produced by a novel abnormality, such as deletion [6], translocation or rearrangement. TWIST1 gene is located on the short arm of chromosome 7 (7p21). Chromosome 7 may also have a ring shape. If the gene is entirely deleted, individuals are at higher risk for intellectual disability.

Since patients with anal malposition or stenosis have been described, the physician should order further investigation, such as computer tomography scanning, contrast enema or colonoscopy, to elucidate the severity of the condition, if the patient is symptomatic for such a condition and clinical judgment dictates.

Intracranial hypertension may also be present in affected individuals [4]. Patients occasionally present with seizures, that could be caused by the increased intracranial pressure or by brain malformations or lesions [7]. In this situation, an electroencephalogram, as well as detailed neuroimaging and neurophysiological studies are indicated.

Women with SCS should undergo regular breast cancer screening due to their increased risk for developing this malignancy [2].

Cranial, spine, and limbs abnormalities are best characterized by computer tomography scanning. An audiogram is indicated when the child develops hearing loss [8].

Prenatal diagnosis is possible and involves testing for a TWIST1 mutation and should be performed in case the fetus is diagnosed with craniosynostosis by ultrasound or a parent suffers from this condition.

Management and treatment Treatment of SCS requires management by a craniofacial team with follow-up until young adulthood. [orpha.net]

Surgical Treatment The treatment of Saethre Chotzen syndrome is focused on correction of the abnormal skull shape and mirrors the treatment of craniosynostosis. Surgical correction is most often done between 6 and 12 months of age. [mercy.net]

Surgical treatment The treatment of Saethre Chotzen syndrome is focused on correction of the abnormal skull shape and mirrors the treatment of craniosynostosis. [med.unc.edu]

Prognosis In most cases, when treated and monitored from an early age, the prognosis is excellent. The documents contained in this web site are presented for information purposes only. [orpha.net]

If monitored and treated from an early age, preferably on a multidisciplinary craniofacial team, the prognosis is good. [ai-online.info]

Antenatal diagnosis Prenatal testing for a TWIST1 mutation is rare, but it can be performed in families with a known mutation or when an ultrasound shows craniosynostosis of unknown etiology. [orpha.net]

The occurrence among 13 siblings of a malformation-mental retardation syndrome and diverse malignancies was investigated for etiologic relationship by clinical, genetic, immunologic, and virologic techniques. [ncbi.nlm.nih.gov]

Epidemiology The incidence of this rare syndrome is estimated at between 1 in 25-50,000 live births. See also Acrocephalosyndactylia External links Article on SCS NIH summary on SCS Template:Multiple abnormalities Template:WH Template:WS [wikidoc.org]

Summary Epidemiology Prevalence ranges from 1/25,000 to 1/50,000 births. Clinical description SCS has a variable spectrum of manifestations. [orpha.net]

Epidemiology The incidence of this rare syndrome is estimated at between 1 in 25-50,000 live births. See also Acrocephalosyndactylia [bionity.com]

Pathophysiology The TWIST1 (Twist Family Basic Helix-Loop-Helix Transcription Factor 1) gene regulates the synthesis of a transcription factor protein that belongs to a large protein family known as basic helix-loop-helix (bHLH) transcription factors [accessanesthesiology.mhmedical.com]

Here, we report 21-bp insertions and nonsense mutations of the TWIST gene (S127X, E130X) in seven ACS III probands and describe impairment of head mesenchyme induction by TWIST as a novel pathophysiological mechanism in human craniosynostoses. [hal.archives-ouvertes.fr]

Here, we report 21-bp insertions and nonsense mutations of the TWIST gene (S127X, E130X) in seven ACS III probands and describe impairment of head mesenchyme induction by TWIST as a novel pathophysiological mechanism in human craniosynostoses. ...read [typeset.io]

This early fusion prevents the skull from growing normally and affects the shape and symmetry of the head and face. [rareguru.com]

This early fusion prevents the skull from growing normally and affects the shape of the head and face. [ghr.nlm.nih.gov]

In Saethre Chotzen syndrome, some of the sutures fuse too soon, preventing the child’s skull from growing normally. [mercy.net]

Saethre-Chotzen syndrome is a genetic disorder in which certain skull bones fuse early and prevent the skull from growing normally. This affects the shape of the head and face. [stlouischildrens.org]

1. Kimonis V, Gold J, Hoffman T, et al. Genetics of craniosynostosis. Semin Pediatr Neurol. 2007;14(3):150-161.
2. Sahlin P, Windh P, Lauritzen C, Emanuelsson M, Gronberg H, Stenman G . Women with Saethre-Chotzen syndrome are at increased risk of breast cancer. Genes Chromosomes Cancer. 2007;46(7):656-660.
3. Preis S, Kaewel EV, Majewski F. Gorlin-Chaudhry-Moss or Saethre-Chotzen syndrome? Clin Genet. 1995;47(5):267-269.
4. Kress W, Schropp C, Lieb G, et al. Saethre-Chotzen syndrome caused by TWIST 1 gene mutations: functional differentiation from Muenke coronal synostosis syndrome. Eur J Hum Genet. 2006;14(1):39-48.
5. Johnson D, Horsley S, Moloney D. 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;63:1282-1293.
6. Chun K, Teebi A, Jung J, et al. Genetic analysis of patients with the Saethre-Chotzen phenotype. Am. J. Med. Genet. 2002;110:136-143.
7. Elia M, Musumeci S, Ferri R, et al. Saethre-Chotzen syndrome: a clinical, EEG and neuroradiological study. Childs Nerv Syst. 1996;12(11):699-704.
8. Rosen H, Andrews B, Meara J, Stoler JM, Mulliken JB, Rogers GF. Audiologic findings in Saethre-Chotzen syndrome. Plast Reconstr Surg. 2011;127(5):2014-2020.