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 (Acrocephalosyndactyly type I)

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 (Acrocephalosyndactyly type II)

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 (Acrocephalosyndactyly type III)

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 (Acrocephalosyndactyly type V)

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: