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]

  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]

  Less common manifestations include short stature, hypertelorism, cleft palate, bifid uvula, maxillary hypoplasia, vertebral anomalies, obstructive sleep apnea and congenital heart malformations. Vertebral fusions and scoliosis occur in rare cases. [orpha.net]

  He has short stature, webbing of his hands, pulmonary stenosis, seizures and hydrocephalus along with developmental delay. [ggc.org]

  stature abnormalities in the bones of the spine hearing loss [3] heart defects Non-physical Symptoms Most patients with this condition have normal intelligence; however, cases of delayed development and learning difficulties have been reported. [pfond.cmmt.ubc.ca]

• 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]

  fingers, joining of the fingers (syndactyly) and broad toes (rarely cause any problems); and fusion of bones in the neck rarely causing problems but care must be taken during anaesthetics. [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]

• 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

  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.

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.