What is Crouzon syndrome? |

Risk Factors

Those most at risk for Crouzon syndrome are children of parents with the disorder, children whose parents do not have the disorder but who carry the gene that causes the disorder, and children whose fathers are at an older age at the time of conception.

Etiology and Genetics

Crouzon syndrome is inherited as an autosomal dominant disorder, meaning that a single copy of the mutation is sufficient to cause full expression of the syndrome. An affected individual has a 50 percent chance of transmitting the mutation to each of his or her children. Many cases of Crouzon syndrome, however, result from a spontaneous new mutation, so in these instances affected individuals will have unaffected parents.

Most individuals with Crouzon syndrome carry a mutation in a gene called FGFR2, which is found on the long arm of chromosome 10 at position 10q26. FGFR2 encodes a protein known as fibroblast growth factor receptor 2. Like many similar receptors, this protein has multiple functions, but one particularly important effect is to signal the appropriate population of stem cells to develop into bone cells during embryonic and fetal development. It is believed that mutations in this gene result in an overstimulation by the receptor protein that can cause the bones of the skull to prematurely fuse.

Mutations in a second gene, FGFR3, found on the short arm of chromosome 4 at position 4p16.3, have also been known to be associated with Crouzon syndrome, although patients with these mutations also exhibit a characteristic skin condition known as acanthosis nigricans (dark, thick, velvety skin in body folds, often in the neck and armpit area). The gene product is another fibroblast growth factor receptor, one that is more commonly associated with achondroplastic dwarfism.

Symptoms

The main signs and symptoms of Crouzon syndrome include flattened top and back of head; flattened forehead and temples; midface that is small and located farther back in the face than normal; beaklike nose; compression of nasal passages, often causing reduced airflow through the nose; a large, protruding lower jaw; misalignment of teeth; and a high-arched, narrow palate, or cleft palate. Other symptoms and complications that can result from Crouzon syndrome include hearing loss, deformity of middle ears, absence of ear canals, Ménière’s disease (dizziness, vertigo, or ringing in the ears), vision problems, crossed eyes or involuntary eye movement, curvature of the spine, headaches, fused joints (in some cases), and acanthosis nigricans (small, dark, velvety patches of skin).

Screening and Diagnosis

A doctor can usually diagnosis Crouzon syndrome at birth or in early childhood based on the patient’s physical signs and symptoms. Tests are taken to confirm the diagnosis. They may include x-rays, a test that uses radiation to take a picture of structures inside the body, especially bones; a magnetic resonance imaging (MRI) scan, a test that uses magnetic waves to make pictures of the inside of the body; and a computed tomography (CT) scan, a type of x-ray that uses a computer to make pictures of the inside of the body. Genetic testing to confirm mutations in the FGFR2 or FGFR3 gene may be used if the clinical findings are not sufficient to make a diagnosis.

Treatment and Therapy

There is no cure yet for Crouzon syndrome. Because the molecular cause is now known, scientists are exploring ways to block the processes that lead to early fusion of the sutures without affecting other important growth processes. These efforts are currently restricted to experimental animals, but human advances may be on the horizon.

Many of the symptoms can be treated with surgery. In addition, orthodontic treatment, eye and ear treatment, and supportive treatment are usually needed. Good dental care is also an important aspect of managing the care of children with Crouzon syndrome.

There are a number of surgeries used to treat the symptoms of Crouzon syndrome. They include craniectomy, which involves removal and replacement of portions of the cranial bone. This surgery is done as early as possible after birth to prevent pressure on and damage to the brain and to maintain a skull shape that is as normal as possible. Surgery to treat exophthalmos (protrusion of one or both eyeballs) is done directly on the eye sockets or on the bones surrounding the eye sockets to help minimize exophthalmos. Surgery to treat protruding lower jaw is often very successful in normalizing the appearance of the jaw by removing a portion of the jawbone. Surgery can also be done to repair a cleft palate.

Braces and other orthodontic treatments are usually necessary to help correct misalignment of teeth. An ophthalmologist (eye specialist) and otolaryngologist (ear, nose, and throat specialist) should monitor infants and children with Crouzon syndrome. These specialists can check for problems and provide corrective treatment as necessary. Supportive treatment for the disease includes special education for children with intellectual disabilities.

Prevention and Outcomes

There is no known way to prevent Crouzon syndrome. If a patient has Crouzon syndrome or has a family history of the disorder, he or she can talk to a genetic counselor when deciding to have children.

Bibliography

Alan, Rick. "Crouzon Syndrome." Health Library. EBSCO, 3 June 2014. Web. 22 July 2014.

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Jones, Kenneth Lyons, Marilyn Crandall Jones, and Miguel del Camp Casanelles. Smith's Recognizable Patterns of Human Malformation. 7th ed. Philadelphia: Elsevier, 2013. Print.

Kelly, Evelyn B. Encyclopedia of Human Genetics and Disease. 2 vols. Santa Barbara: Greenwood, 2013. Print.

Kjaer, I., et al. “Abnormal Timing in the Prenatal Ossification of Vertebral Column and Hand in Crouzon Syndrome.” American Journal of Medical Genetics 90.5 (2000): 386–89. Print.

Perlyn C. A., et al. “A Model for the Pharmacological Treatment of Crouzon Syndrome.” Neurosurgery 59.1 (2006): 210–15. Print.