1. Background

• first described by O. Crouzon in 1912
• also called Craniofacial Dysostosis

2. Genetic Defect

• genetic defect -> premature synostosis of the coronal, sagittal, and occasionally the lambdoidal sutures beginning in the first year of life and completed by 2-3 years of age
• a mutation in the fibroblast growth factor receptor-2 gene as the cause of Crouzon Syndrome was first reported by Reardon et al. in September 1994 (Nature Genetics 8: 98; 1994)
• mutations of FGFR2 involve exon 7 resulting in changes in only one of the multiple tissue specific isoforms - the one preferentially expressed in the osteogenesis of the frontal bones of the skull (Muenke et al., Nature Genetics 8:269; 1994)
• four different human fibroblast growth factor receptor (FGFR) genes have been cloned and characterized and all four encode tyrosine kinase receptors each having three Ig extracellular domains, one transmembrane segment, and a cytoplasmic tyrosine kinase domain
• mutations within the different receptors result in various disorders: hFGFR Disorder
  1 Pfeiffer Syndrome
  2 Crouzon Syndrome Jackson-Weiss Syndrome
  3 Achondroplasia
• the order and rate of suture fusion determines the degree of deformity and disability
• the lack of syndactyly differentiates Crouzon Syndrome from the Acrocephalosyndactyly and Acrocephalopolysyndactyly Syndromes - high penetrance with variable degree of expressivity

1. Craniosynostosis

• coronal and sagittal sutures most commonly involved producing:
  • acrocephaly (cone-shaped head)
  • brachycephaly (shortened A-P diameter)
  • palpable ridging
  • flat occiput
  • high prominent forehead +/- frontal bossing

2. Facial Features

• flattened face with maxillary hypoplasia
• relative mandibular prognathism
• ears
  • low set
  • conductive hearing loss (bilateral atresia of the auditory meatus)
• ocular
  • downslanting palpebral fissure
  • exophthalmos with shallow orbits
  • iris coloboma
  • ptosis
  • exposure conjunctivitis or keratitis
  • decreased visual acuity (optic nerve damage)
  • hypertelorism
  • strabismus (divergent)
  • nystagmus
• nose
  • beaked (psitticorhina)
  • deviated nasal septum +/- nasal airway obstruction
• mouth
  • short upper lip +/- cleft lip
  • class III malocclusion with maxillary crowding
  • high-arched narrow palate +/- cleft palate
  • bifid uvula

3. Other Features

1. Imaging Studies

1. Supportive

• no treatment for underlying disorder
• multidisciplinary approach
  • Paediatrics, Orthopedics, Neurology, Neurosurgery
• genetic counselling
  • recurrence risk is not elevated with unaffected parents but
  • 50% with one affected parent

2. Surgery

• surgical repair of:
  • craniosynostosis - craniotomy
  • facial dysmorphisms - cosmetic reconstruction

3. Prognosis

• morbidity depends upon the severity of the condition
• normal life span