Crouzon syndrome is an autosomal dominant genetic disorder caused by a mutation in a gene on chromosome 10 that controls the body's production of fibroblast growth factor receptor 2 (FGFR2). Crouzon syndrome is named for Octave Crouzon, a French physician who first described this disorder. First called "craniofacial dysostosis" ("craniofacial" refers to the skull and face, and "dysostosis" refers to malformation of bone), the disorder was characterized by a number of clinical features which can be described by the rudimentary meanings of its former name. The developing fetus's skull and facial bones fuse early or are unable to expand. Thus, normal bone growth cannot occur. Fusion of different sutures leads to abnormal patterns of growth of the skull.

Signs and symptoms

thumb|Child with Crouzon syndrome showing characteristic facial features.

thumb|left|Cranial sutures

A defining characteristic of Crouzon syndrome is craniosynostosis, which results in an abnormal head shape. This is present in combinations of: frontal bossing, trigonocephaly (fusion of the metopic suture), brachycephaly (fusion of the coronal suture), dolichocephaly (fusion of the sagittal suture), plagiocephaly (unilateral premature closure of lambdoid and coronal sutures), oxycephaly (fusion of coronal and lambdoidal sutures), and complex craniosynostosis (premature closure of some or all sutures).

Exophthalmos (bulging eyes due to shallow eye sockets after early fusion of surrounding bones), hypertelorism (greater than normal distance between the eyes), and psittichorhina (beak-like nose) are also very common features. Other facial characteristics that are present in many cases include external strabismus and hypoplastic maxilla (insufficient growth of the midface), which results in relative mandibular prognathism (protruding chin) and gives the effect of the patient having a concave face.

Most symptoms are secondary to the abnormal skull structure. Approximately 30% of people with Crouzon syndrome develop hydrocephalus. Sensorineural hearing loss is present in some cases. The abnormalities in the manner in which the eyes fit in the eye sockets can cause vision problems, the most common of which is corneal exposure that can lead to visual impairment. Some people with the condition have a restricted airway and can experience severe problems breathing.

Common features are a narrow/high-arched palate, posterior bilateral crossbite, hypodontia (missing some teeth), and crowding of teeth. Due to maxillary hypoplasia, people with Crouzon syndrome generally have a considerable permanent underbite.

Causes

The current research indicates fibroblast growth factor receptors (FGFR) FGFR2 and FGFR3 as the leading factors in causing the autosomal dominant Crouzon syndrome. FGFR2 is the most commonly mutated gene, a missense at cysteine 342 in exon 9, which creates a gain-of-function. resulting in premature fusion of frontal cranial bones. It is the most common craniostenosis syndrome.

History

Crouzon syndrome was first described by Octave Crouzon in 1912. He noted the affected patients were a mother and her daughter, implying a genetic basis.

See also

  • Apert syndrome
  • Treacher Collins syndrome
  • Hearing loss with craniofacial syndromes

References

  • Crouzon syndrome on Genetics Home Reference from U.S. National Library of Medicine & National Institutes of Health
  • GeneReviews/NIH/NCBI/UW entry on FGFR-Related Craniosynostosis Syndromes