Saethre-Chotzen Syndrome

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.

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.