Genetics of Crouzon Syndrome

Updated: May 06, 2015
  • Author: Harold Chen, MD, MS, FAAP, FACMG; Chief Editor: Maria Descartes, MD  more...
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Overview

Background

In 1912, Crouzon described the hereditary syndrome of craniofacial dysostosis in a mother and son. He described the triad of calvarial deformities, facial anomalies, and exophthalmos.

Crouzon syndrome is an autosomal dominant disorder with complete penetrance and variable expressivity. [1] It is characterized by premature closure of calvarial and cranial base sutures as well as those of the orbit and maxillary complex (craniosynostosis).

Other clinical features include hypertelorism, exophthalmos, strabismus, beaked nose, short upper lip, hypoplastic maxilla, and relative mandibular prognathism. Unlike some other forms of autosomal dominant craniosynostosis, no digital abnormalities are present. See the image below.

Child with Crouzon syndrome. Note midfacial hypopl Child with Crouzon syndrome. Note midfacial hypoplasia, proptosis secondary to shallow orbits, and ocular hypertelorism.
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Pathophysiology

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  • Crouzon syndrome is caused by mutations in the fibroblast growth factor receptor-2 ( FGFR2) gene but exhibits locus heterogeneity with causal mutations in FGFR2 (Crouzon syndrome) and FGFR3 (Crouzon syndrome with acanthosis nigricans) in different affected individuals.
  • Premature synostosis of the coronal, the sagittal, and, occasionally, the lambdoidal sutures begins in the first year of life and is completed by the second or third year. The order and rate of suture fusion determine the degree of deformity and disability. Once a suture becomes fused, growth perpendicular to that suture becomes restricted, and the fused bones act as a single bony structure. Compensatory growth occurs at the remaining open sutures to allow continued brain growth. However, multiple sutural synostoses frequently extend to premature fusion of the skull base sutures, causing midfacial hypoplasia, shallow orbits, a foreshortened nasal dorsum, maxillary hypoplasia, and occasional upper airway obstruction.
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Epidemiology

Frequency

United States

  • Prevalence is 1 case per 60,000 (approximately 16.5 cases per million population) live births. [2]
  • Crouzon syndrome is responsible for approximately 4.8% of all cases of craniosynostosis.

Mortality/Morbidity

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  • Upper airway obstruction can lead to acute respiratory distress.
  • Increased intracranial pressure and optic atrophy may occur.

Race

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  • Crouzon syndrome has no race predilection.

Sex

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  • Crouzon syndrome has no known sex predilection.

Age

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  • The condition is detected in the newborn or infant period because of dysmorphic features.
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