Craniofacial conditions

Saethre-Chotzen Syndrome

Common syndromic craniosynostosis with involvement of the coronal sutures, drooping eyelids and a characteristic ear shape.

Summary

Saethre-Chotzen syndrome is one of the more common syndromic craniosynostoses. It is caused by a change in the TWIST1 gene. Typical features are premature closure of one or both coronal sutures, drooping upper eyelids (ptosis), a low frontal hairline as well as small, characteristically shaped ears. Intellectual development is usually normal. Long-term monitoring of intracranial pressure is important, as raised pressure can recur after operations.

Cause & genetics

Cause and inheritance

The cause is changes (mutations or deletions) in the TWIST1 gene on chromosome 7p21.^[1] Inheritance is autosomal dominant with very variable expression – even within a family the picture can vary greatly. If the syndrome arises through a larger deletion that also affects neighbouring genes, a developmental delay may additionally be present. The frequency is estimated at about 1 : 25,000 to 1 : 50,000.

Genetic counselling: in every uni- or bilateral coronal suture synostosis with syndromic signs, a TWIST1 analysis should be carried out – the recurrence and complication risk differs from the non-syndromic form.^[2]

Features

Typical features

Uni- or bilateral coronal suture synostosis (facial asymmetry in the unilateral form)
Drooping upper eyelids (ptosis)
Low frontal hairline
Small, rounded ears with a prominent cartilage ridge (prominent crus)
Wide eye spacing (hypertelorism), narrow palpebral fissures
Short fingers (brachydactyly) and slight skin fusions between fingers (cutaneous syndactyly, often fingers 2–3)
Palate anomalies in a proportion of cases

The features are often more subtle than in Apert or Crouzon syndrome. Individual assessment is decisive.

Intracranial pressure

Raised intracranial pressure and re-operations

A particularity of Saethre-Chotzen syndrome is the increased likelihood, compared with non-syndromic synostosis, of recurrent intracranial hypertension after the first operation. In a 15-year review from a specialised centre, 35–42 % of children required a further skull operation due to recurrent raised intracranial pressure; values from other centres may differ.^[2] Regular ophthalmological and clinical checks throughout childhood are therefore important.

Why follow-up matters: raised intracranial pressure can persist for a long time without clear complaints. Regular fundus checks help to detect it in time.

Surgery

Craniofacial procedures

Skull surgery is in the foreground, in particular fronto-orbital advancement with remodelling of the forehead and orbital rim in the first year of life. The aim is sufficient room for the brain, lowering of intracranial pressure and a balanced forehead/orbit shape. In unilateral synostosis the asymmetry is corrected. A midface advancement (Le Fort III) is less often needed than in Apert/Crouzon, but may become necessary in case of marked midface involvement. Drooping upper eyelids are corrected ophthalmologically/surgically in case of functional visual impairment.

Eyes & hearing

Eyes, hearing and development

Besides ptosis, visual defects and – with raised intracranial pressure – a risk to the optic nerve can occur; regular ophthalmological checks are important. Middle-ear problems and hearing loss occur and should be monitored. Intellectual development is normal in most children; a delay is possible mainly with larger gene deletions.

Diagnostics

The work-up includes: clinical examination by a craniofacial team, genetic testing of the TWIST1 gene (including a search for deletions), 3D imaging of the skull, ophthalmological examination with fundus assessment as well as ENT examination and hearing test.

Interdisciplinary

Treatment in an interdisciplinary centre

Ideal is care by a team with craniofacial surgery / oral and maxillofacial surgery, neurosurgery, ophthalmology, ENT, orthodontics, paediatrics, genetics, speech therapy and psychology.

Treatment roadmap

Possible treatment roadmap

Newborn period

Confirmation of the diagnosis, assessment of skull shape, eyes and hearing, genetic work-up.

1st year of life

Fronto-orbital advancement / skull remodelling in case of relevant synostosis.

Toddler / childhood

Regular monitoring of intracranial pressure (fundus), if needed correction of the ptosis, orthodontic support.

Adolescence

If needed, midface / bite correction, psychosocial support, transition to adult medicine.

Warning signs

When medical help is needed

Increasing headaches, vomiting, unusual irritability or visual disturbances (sign of intracranial pressure)
Marked visual impairment due to drooping eyelids
Fever or wound problems after operations

Prognosis

The prognosis is overall favourable: most children develop normally and lead an active life. The individual course can however vary. Decisive are the rigorous control of intracranial pressure and long-term interdisciplinary follow-up.

Key message: Saethre-Chotzen syndrome (TWIST1) often runs a milder course than other syndromic craniosynostoses but, because of the risk of recurrent intracranial hypertension, requires careful, long-term follow-up at a specialised centre.

References

Zackai EH, Stolle CA (1998). A new twist: some patients with Saethre-Chotzen syndrome have a microdeletion syndrome. Am J Hum Genet, 63(5):1277–81. DOI
Woods RH, Ul-Haq E, Wilkie AOM, et al. (2009). Reoperation for intracranial hypertension in TWIST1-confirmed Saethre-Chotzen syndrome: a 15-year review. Plast Reconstr Surg, 123(6):1801–1810. DOI
Renier D, Lajeunie E, Arnaud E, Marchac D (2000). Management of craniosynostoses. Childs Nerv Syst, 16(10–11):645–58. DOI