Syndromic craniosynothosis

• Severity
• Mild cases
• No functional complications
• Management
• Conservative
• Surgical treatment
• Indication
• Cosmesis
• Defer definitive surgery until growth is complete
• Reducing pschological impact of deformity
• Severe cases
• Management
• Surgery
• indication
• Aim to preserve function by managing complication associated with
• Airway
• ICP
• Exorbitism
• Failure to thrive
• Cosmesis
• Defer definitive surgery until growth is complete
• Reducing psychological impact of deformity

• Associated tumour types
• Craniopharyngiomas (6-9%)
• Optic Pathway Hypothalamic Astrocytomas (2-7%)
• Germinomas (3%)
• Pituitary Adenomas (1-2%)
• Dermoids / Epidermoids
• Other:
• Meningiomas
• Haemangiomas
• Ependymomas
• Schwannomas
• Cavernomas

Muenke’s syndrome

• Unicoronal or bicoronal craniosynostosis

• Brachydactyly

• Thimble-like middle phalanges

• Coned epiphyses

• Carpal and tarsal fusions

• Sensorineural hearing loss

• Developmental delay

• Learning difficulties

• Seizures

• FGFR3

• Autosomal dominant.

• Caused by a point mutation in Pr0250Arg in the Ig 11-111 linker region of the FGFR3 gene on chromosome 4p16.3

 

Abnormal skull shape
Low risk of raised ICP

 

Saethre-Chotzen syndrome

• Manifestations very variable → need genetic testing

• Coronal craniosynostosis with limb abnormalities (syndactyly of the second and third digits, bifid hallux)

• Facial abnormalities (facial asymmetry, low frontal hairline, ptosis, and small ears with prominent ear crura)

• TWIST1 Chr 7

• Autosomal dominant with complete penetrance and variable expressivity.

• Caused by loss-of-function mutations in TWIST (missense, nonsense, deletions, insertions, and duplications). Report of Q289P mutation in FGFR2

Abnormal skull shape Risk of ICP.

 

Crouzon’s syndrome

• Most common

• Classical triad
• Coronal synostosis
• Midfacial hypoplasia
• Exophthalmos

• Other features
• May also include involvement of other calvarial sutures
• Brachycephaly
• Hypertelorism
• Chiari I malformation
• Hydrocephalus
• Mental retardation

• FGFR2 Chr 10

• Autosomal dominant.

• Caused by numerous missense mutations in the Ig 111 domain of the FGFR2 gene (many involve the gain or loss of a cysteine residue)

 

Abnormal skull shape Risk of ICP.

 

Pfeiffer’s syndrome

• Classical features
• brachycephaly
• membranous syndactyly of hands and feet with enlarged and deviated thumbs and great toes

• Types
• Type I classical Pfeiffer’s syndrome is a mild entity
• Types II and III are more severe, with early death.

• Other features
• Coronal synostosis with or without premature fusion of other calvarial sutures
• Cloverleaf skull
• Facial
• maxillary hypoplasia
• small nose with a low nasal bridge
• hypertelorism
• shallow orbits
• proptosis
• strabismus
• limb malformation
• Radiohumeral synostosis
• Broad fingers and toes
• partial syndactyly of the fingers and toes

• FGFR1, FGFR2

• Type I: autosomal dominant.
• Caused by FGFR1mutations, including Pr0252Arg in the Ig II-III linker region on chromosome 8p11.2-p11.
• Can also be caused by mutations in FGFR2 and be associated with more severe phenotypic expression.

• Types II and III: sporadic inheritance.

 

Apert’s syndrome (Acrocephalosyndactyly)

• 2nd most common

• Features
• Bicoronal synostosis
• Severe polysyndactyly in the fingers and toes
• Symphalangism (fusion of the phalanges)
• Radiohumeral fusion
• Mental retardation (IQ can be normal or mildly reduced)
• Antimongoloid slanted eyes
• Maxillary hypoplasia
• Cheerful effect

• Vs Crouzon's at the faciocranial level
• is the presence of hypertelorism and an open bite, in which the anterior part of the maxillary alveolar arch is higher than the posterior part.
• The face and the forehead are also abnormally wide, and the anterior fontanelle is widely open during the first months of life.

 

• FGFR2

• Autosomal dominant.

• Caused by a number of different mutations in FGFR2 on chromosome 10q26, including two missense mutations (Ser252Trp, Pr0253Arg) and two Alu insertions

 

Abnormal skull shape Risk of ICP.

Jackson-Weiss syndrome