About crouzon craniofacial dysostosis

What is crouzon craniofacial dysostosis?

Crouzon syndrome is a rare genetic disorder that may be evident at birth (congenital) or during infancy. The disorder is characterized by distinctive malformations of the skull and facial (craniofacial) region. Such abnormalities may vary greatly in range and severity from case to case, including among affected family members. However, in most infants with Crouzon syndrome, the fibrous joints between certain bones of the skull (cranial sutures) close prematurely (craniosynostosis). In addition, facial abnormalities typically include unusual bulging or protrusion of the eyeballs (proptosis) due to shallow eye cavities (orbits); outward deviation of one of the eyes (divergent strabismus or exotropia); widely spaced eyes (ocular hypertelorism); and a small, underdeveloped upper jaw (hypoplastic maxilla), with protrusion of the lower jaw (relative mandibular prognathism).

In some instances, Crouzon syndrome is inherited as an autosomal dominant trait. In other cases, affected individuals have no family history of the disease. In such instances, Crouzon syndrome is thought to result from new genetic changes (mutations) that occur randomly for unknown reasons (sporadically).

What are the symptoms for crouzon craniofacial dysostosis?

Crouzon syndrome, also known as Craniofacial dysostosis, is primarily characterized by premature closure of the fibrous joints (cranial sutures) between certain bones in the skull (craniosynostosis) and distinctive facial abnormalities. Cranial and facial malformations may vary, ranging from mild to potentially severe, including among members of the same family (kindred).

For example, the degree of cranial malformation is variable and depends on the specific cranial sutures involved as well as the order and rate of progression. In most affected individuals, there is premature fusion of the sutures (i.e., coronal and sagittal sutures) between bones forming the forehead (frontal bone) and the upper sides of the skull (parietal bones). In addition, the suture between the back and the sides of the skull (i.e., lambdoidal suture) or other sutures may be involved in some people. In most individuals with Crouzon syndrome, early sutural fusion causes the head to appear unusually Short and broad (brachycephaly). In other patients, the head may appear long and narrow (scaphocephaly) or triangular (trigonocephaly). Rarely, premature closure of multiple sutures (known as Kleeblattschadel type craniosynostosis) causes the skull to be abnormally divided into three lobes (cloverleaf skull deformity). In those with Crouzon syndrome, craniosynostosis typically begins during the first year of life and progresses until approximately age two to three. However, craniosynostosis may sometimes be apparent at birth or, more rarely, may not be noted during early childhood.

In most individuals, there is unusual shallowness of the orbits or the bony cavities of the skull that accommodate the eyeballs. As a result, the eyeballs appear to protrude or bulge forward (proptosis). Due to such abnormalities, affected individuals are unusually susceptible to developing inflammation of the front, transparent regions of the eyes (i.e., exposure keratitis) as well as the membranes that line the inner surfaces of the eyelids and cover the Whites of the eyes (exposure conjunctivitis). Crouzon syndrome is also often associated with additional eye abnormalities including eyes that are spaced apart wider than usual (hypertelorism) and eyes that are crossed or do not point in the same direction (strabismus). Sometimes, the various eye abnormalities can lead to a loss in vision.

Crouzon syndrome is associated with additional Craniofacial abnormalities. Affected individuals often have a prominent forehead (frontal bossing); a curved nose; unusually flat or underdeveloped mid-facial regions (midface hypoplasia); and a Short upper lip. In addition, a small, Underdeveloped upper jaw (hypoplastic maxilla) with protrusion of the lower jaw (relative mandibular prognathism) may also occur. Clefting of the lip and/or palate (incomplete closure of the palate or an abnormal groove in the upper lip) can occur rarely. Typical dental problems include a highly arched narrow palate with crowded teeth, and upper and lower teeth that don’t meet when biting (malocclusion).

Approximately 30% of individuals with Crouzon syndrome develop hydrocephalus, a condition which is characterized by impaired flow or absorption of the fluid (i.e., cerebrospinal fluid [CSF]) that circulates through cavities (ventricles) of the brain and the spinal canal, potentially leading to increasing fluid pressure within the skull (intracranial pressure) and the brain and other associated findings.

Some affected individuals have Hearing impairment due to an inability to transmit sound impulses to the brain (sensorineural hearing loss). In some infants, Breathing problems may occur in infancy due to various abnormalities of the face and upper airway. In severe instances, this can lead to life-threatening breathing complications.

What are the causes for crouzon craniofacial dysostosis?

Crouzon syndrome is caused by alterations (mutations) in one of the FGFR genes, most commonly FGFR2. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body.

The alterations in the FGFR gene that cause Crouzon syndrome are inherited in an autosomal dominant manner. Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.

In most individuals, the disorder occurs because of spontaneous (de novo) genetic mutations that occur in the egg or sperm cell. In such situations, the disorder is not inherited from the parents.

The FGFR2 gene regulates the production of a protein known as a fibroblast growth factor receptor (FGFR). Genetic mutations that disrupt the functioning of such proteins may result in abnormalities of bone growth and development, ultimately leading to certain malformations of the craniofacial area. Evidence indicates that different mutations in the FGFR2 gene may cause a number of other related disorders, including Apert syndrome, isolated coronal synostosis, Beare-Stevenson syndrome, Pfeiffer syndrome, and Jackson-Weiss syndrome. In addition, according to some reports, certain FGFR2 mutations may result in Crouzon syndrome in some families (kindreds), whereas the same mutations cause Pfeiffer syndrome in other kindreds. The implications of such findings are not completely understood. 

What are the treatments for crouzon craniofacial dysostosis?

The treatment of Crouzon syndrome is directed toward the specific symptoms that are apparent in each individual. Surgery is the main form of therapy for affected children, but not all children will require surgery. Surgery is performed to create and ensure that there is enough room within the skull for the developing brain to grow; to relieve intracranial pressure (if present); and to improve the appearance of an affected child’s head.

What are the risk factors for crouzon craniofacial dysostosis?

Risk factors for crouzon craniofacial dysostosis:

1. One of the FGFR genes, usually FGFR2, changes (mutations) lead to Crouzon syndrome. The instructions for making proteins, which are essential to numerous bodily processes, are provided by genes.
2. A gene mutation might result in the production of a protein that is defective, ineffective, or nonexistent. This can have an impact on a variety of body organ systems depending on the specific protein's functions.
3. Crouzon syndrome is inherited via autosomal dominant means due to changes in the FGFR gene. The condition of the two copies of a gene, one acquired from the father and one from the mother, determines the majority of genetic illnesses.
4. When a single copy of a defective gene is required to induce a specific disease, dominant genetic diseases result. The faulty gene may be brought on by a new mutation (gene alteration) in the sick person or it may be inherited from either parent.
5. For every pregnancy, there is a 50% chance that the defective gene will be passed from a parent who is affected to the child. Both men and women are at the same level of danger.
6. The illness is most frequently brought on by spontaneous (de novo) genetic changes in the sperm or egg cell. In these cases, the illness is not passed down from one's parents.

Premature closure of the fibrous joints,Distinctive facial abnormalities
Hypertelorism,Exposure conjunctivitis

Is there a cure/medications for crouzon craniofacial dysostosis?

Affected children should be seen at craniofacial clinics, which are often affiliated with major pediatric hospitals or medical centers. These clinics have a team of physicians and other healthcare providers who are experienced in treating craniofacial disorders. A team of specialists will work together to plan and carry out a child’s treatments. Such specialists include pediatricians, neurosurgeons, plastic surgeons, otolaryngologists, medical geneticists, audiologists, ophthalmologists, dental specialists, social workers, and other healthcare professionals. Genetic evaluation may be of benefit for affected individuals and their families to confirm the diagnosis and offer counseling. Psychosocial support for the entire family is essential as well.

Video related to crouzon craniofacial dysostosis