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

  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]

  stature Heart defects Hearing loss Abnormalities of the vertebra Treatment for Saethre-Chotzen syndrome: Treatment for Saethre-Chotzen syndrome is usually multiple-staged surgery. [dellchildrens.net]

  […] 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]

  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. [symptoma.com]

• 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]

  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]

  […] 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]

  Some characteristic traits of children with Saethre-Chotzen syndrome: irregular head growth droopy eyelids wide-set eyes beaked nose crossed eyes (strabismus and amblyyopia) short fingers and /or toes (some may be fused) low hairline Most children with [childrenshospital.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]

• Single Transverse Palmar Crease

  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 [symptoma.com]

  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 [rarediseases.info.nih.gov]

• Skull Disorder

  Abstract Saethre-Chotzen syndrome is an autosomal dominant skull disorder resulting from premature fusion of coronal sutures (craniosynostosis). It is caused by mutations in the TWIST gene encoding a basic Helix-Loop-Helix transcription factor. [ncbi.nlm.nih.gov]

• Hearing Impairment

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

  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]

  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

  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]

  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]

• 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]

  Some characteristic traits of children with Saethre-Chotzen syndrome: irregular head growth droopy eyelids wide-set eyes beaked nose crossed eyes (strabismus and amblyyopia) short fingers and /or toes (some may be fused) low hairline Most children with [childrenshospital.org]

  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]

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]

Our doctors, surgeons and the rest of the staff are extremely knowledgeable and always up to date on the newest methods of diagnosis and treatment. [craniofacial.net]

Because every patient with Seathre-Chotzen syndrome has unique problems, the timing and course of surgical treatment is highly individualized. [chop.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]

Prognosis The survival rate is good, with frequent reports of survival to adulthood. Affected children suffer from developmental delay, growth retardation and feeding difficulties. [natureblind.blogspot.com]

[…] de novo (new) mutation or deletions of the ZEB2 (also known as ZFHX1B or SMADIP1) gene on chromosome 2q22. [ 3 ] However, some of those affected by the disease do not have abnormalities of this gene that are currently detectable. [ citation needed ] Prognosis [en.academic.ru]

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]

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]

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

A malformation syndrome characterised by facial abnormalities, broad thumbs, broad great toes, short stature, and mental retardation. 1 It was first described in 1963 by Rubinstein and Taybi. 2 Epidemiology Incidence is about 1 case per 100,000 live births [natureblind.blogspot.com]

Epidemiology Pfeiffer syndrome affects about 1 in 100,000 individuals. Clinical description A craniosynostosis in association with short, broad thumbs and big toes are the major diagnostic clues for Pfeiffer syndrome. [ojrd.biomedcentral.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. [ncbi.nlm.nih.gov]

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]

It’s a condition which prevents the skull from growing normally due to premature fusion of certain skull bones. [grinerplasticsurgery.com]

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

Saethre-Chotzen syndrome is one of many disorders that results in these sutures closing early and preventing the skull from growing properly. What causes Saethre-Chotzen syndrome? Saethre-Chotzen syndrome is caused by genetic mutations. [nicklauschildrens.org]

Saethre-Chotzen syndrome is a genetic condition characterized by the premature fusion of certain skull bones, which prevents the skull from growing normally and affects the shape of the head and face. [childrenshospital.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.