Syndromic craniosynostosis

There are reported more than 90 syndromes associated with craniosynostosis. Most of these are also associated with other anomalies of the limbs, ears, and cardiovascular system. The syndromes which are most commonly encountered by surgeons are the :

• Apert syndrome
• Crouzon syndrome
• Pfeiffer syndrome
• Saethre-Chotzen syndrome
• Muenke syndrome

A cardinal feature of the syndromic cranial synostosis is:

• midface hypoplasia
• exorbitism
• forehead retrusion

Most of these patients have bicoronal synostosis but multiple cranial sutures in different combinations may be involved.

Clover leaf skull or Kleeblattschädel, is seen in any of the syndromes listed above and is characterized by closure of all cranial sutures except sagittal and squamosal.

To the left, the appearance of the "Beaten Copper Cranium" pattern in a CT-scan of a patient with a clover leaf skull deformity.

Apert syndrome is caused by a mutation in the FGFR2 gene and occurs sporadically, but can be inherited in an autosomal dominant fashion.

Apert syndrome is reported in 1:160,000 live births.

The Apert syndrome is characterized by:

• Bicoronal or multiple suture synostosis
• Exorbitism
• Midface hypoplasia
• Maxillary hypoplasia with Class III malocclusion
• Mild hypertelorism
• Complex syndactyly of the fingers and toes
• Cleft palate (30%), high arched palate
• CNS malformations – macrocephaly, hydrocephalus (5-10%), developmental delay and lowered IQ

Crouzon syndrome is caused by a mutation in the FGFR2 gene and inherited in an autosomal dominant fashion.

Cruzon syndrome is reported in 1:25,000 live births.

The Crouzon syndrome is characterized by:

• Bicoronal (or multiple suture) synostosis
• Midface hypoplasia
• Maxillary hypoplasia with Class III malocclusion
• Exorbitism
• Absence of limb anomalies is a defining characteristic

Saethre-Chotzen syndrome is caused by mutations in the TWIST1 gene, and is inherited in an autosomal dominant fashion.

Saethre-Chotzen syndrome is reported in 1:25,000 – 1:50,000 live births.

The Saethre-Chotzen syndrome is characterized by:

• Bicoronal synostosis
• Skull asymmetry
• Maxillary hypoplasia with a narrow palate (not typically midface retrusion)
• Low set hairline
• Ptosis of the eyelids
• Ear anomalies
• Incomplete simple syndactyly of the index and middle fingers and the 3rd and 4th toes
• Typically normal intelligence

Pfeiffer syndrome is linked to a mutation in in both the FGFR1 (5-10 %) and the FGFR2 (90-95%) gene and is inherited in an autosomal dominant fashion with incomplete penetrance.

Pfeiffer syndrome is reported in 1:100,000 live births.

Pfeiffer syndrome is characterized by:

• Bicoronal or multiple suture synostosis
• Maxillary hypoplasia
• Exorbitism
• Hypertelorism
• Broad thumbs and toes
• IQ varying from normal to severely impaired

Muenke syndrome is linked to a mutation in the FGFR3 gene and is inherited as an autosomal dominant trait.

Muenke syndrome is reported in 1:50'000 live births.

Muenke syndrome is characterized by:

• Bi- or uni-coronal suture synostosis
• Mild or no midface hypoplasia
• Typically normal intelligence