Crouzon syndrome, also known as Crouzon’s disease, is one of several known genetic craniosynostoses in which the cranial sutures ossify prematurely, resulting in impaired skull growth and typical deformities and growths on the head and face. The mental development of people affected by Crouzon syndrome is usually normal.
What is Crouzon syndrome?
Crouzon syndrome, also called dysostosis craniofazialis Crouzon, is one of several known craniosynostoses. The condition is characterized by early ossifications of the cranial sutures, some of which begin prenatally. The ossifications lead to the fact that the brain during its growth phase cannot easily spread under the normally also “growing” skullcap. Instead, the skull cap grows predominantly at the not yet ossified cranial sutures, so that typical malformations occur if left untreated. In Crouzon syndrome, the coronal, alpha and sagittal sutures ossify first. Without treatment or corrective surgery, a typical tower skull is formed and facial anomalies such as overly wide eyes (hypertelorism) and strongly protruding eyes (exophthalmos) occur. In addition to malocclusions of the teeth, hearing loss must be expected in Crouzon syndrome because the external auditory canal has an obstruction, an auditory canal atresia, and/or the auditory ossicles are not fully formed, resulting in impaired hearing.
Causes
Crouzon syndrome is caused exclusively by a mutation at gene locus 10q26 on chromosome 10. There are approximately 1,200 genes on chromosome 10, which contain 4% to 4.5% of human cell DNA. Gene 10q26 is responsible for encoding “fibroblast growth factor receptor 2” (FGFR2). The effects of this specific gene mutation vary within an observed range. The gene mutation is inherited in an autosomal dominant manner. This means that Crouzon syndrome is not sex-specific, i.e., it can affect males and females equally, and it means that the disease occurs in any case, even if only one parent is affected by the gene defect at locus 10q26. The most striking effect of this genetic defect is the premature ossification of the cranial sutures. The cranial sutures represent the growth plates of the frontal bone (Os frontale), parietal bone (Os parietale) and occipital bone (Os occipitale). When the sutures ossify during the growth phase, the skull cannot enlarge uniformly and the brain causes increasing growth pressure, resulting in the typical deformations of the cranial dome.
Symptoms, complaints and signs
In addition to the particularly noticeable symptoms of Crouzon syndrome already described above, such as the towering skull, protruding eyes and wide interocular distance, there are other signs that indicate the presence of Crouzon syndrome. These are the protruding ossified cranial sutures, squint of the eyes and strabismus. Strabismus is a coordination weakness of the eye muscles. The eyes cannot be guided parallel or aligned to a common object. Hypoplasia of the upper jaw and a protruding lower lip are also among the symptoms associated with Crouzon syndrome. Symptomatic of maxillary hypoplasia, also called maxillary retrognathia, is the chin protruding far from the upper jaw. The overall picture is one of a concave appearing facial expression. As a rule, the symptomatic manifestations of Crouzon syndrome are not limited to the skull, but other “associated” problems present themselves. Notable among these are humero-radial synostosis, a partial ossification in the shoulder joint, and a subluxation in the elbow joint.
Diagnosis and course
Suspicion of the possible presence of Crouzon syndrome may arise prenatally based on family history. The externally visible symptoms make diagnostic imaging procedures virtually unnecessary. If there is any doubt as to whether Crouzon syndrome is present, a genetic analysis can provide information. The course of the disease varies from individual to individual, especially in associated syndromes. If the disease is not treated, the main symptoms occur mainly during the main growth phase of the skull and brain.After completion of the growth phase, the clearly visible deformities on the head and face remain for life unless surgical intervention is performed.
Complications
In Crouzon syndrome, the formation of the skull in particular is usually severely affected, resulting in ossification of the cranial sutures. This can result in enormous deformities of the head that severely affect the patient’s appearance. Most affected individuals suffer from lowered self-esteem and do not feel attractive. Crouzon syndrome can also lead to social difficulties, which is especially the case in children and young people. The altered appearance can lead to bullying. Mental development is not affected by Crouzon syndrome in most cases. The eyes are also affected by Crouzon syndrome, so that strabismus can occur in this case. This leads to difficulties in coordination. Complications will occur if Crouzon syndrome is not treated surgically in childhood. The treatment itself is only possible as a surgical measure and is primarily aimed at correcting the malformations. In particular, space is made for the growing brain. However, a complete cure of the syndrome is not possible. There is no reduced life expectancy as long as no particular complications arise in the course of the operation.
When should you see a doctor?
In most cases, Crouzon syndrome is detected immediately after birth or even before birth, so additional diagnosis is not necessary in most cases with it. However, a doctor should be consulted to treat the individual complaints and malformations. Especially if the child is squinting, a doctor should be consulted to correct this complaint. Furthermore, the muscles in the face can also be affected by Crouzon syndrome, so that a visit to the doctor is necessary if the patient cannot form an independent facial expression. Ossification at the joints may also indicate the syndrome and must be examined. Usually, the symptoms can be examined and diagnosed by a pediatrician or by a general practitioner. Further treatment depends on the severity of the symptoms, so surgical intervention may be necessary. If the child or the relatives and parents experience psychological discomfort due to Crouzon syndrome, a psychologist should also be consulted to avoid further discomfort and complications.
Treatment and therapy
Treatment of Crouzon syndrome consists essentially of surgical-corrective measures, if needed at all. Three different surgical techniques are known and are offered by specialized clinics. Frontoorbital advancement consists of sawing out the anterior cranial vault, including the forehead, inside the skull and re-fixing it in such a way as to give the brain room for the necessary growth. Reattachment of the skull can basically be done using titanium plates, an absorbable plate system, or absorbable sutures. Which method is used depends on the conditions found during the operation. Operations on the bony facial skull are usually more complex and are referred to as Le Fort III osteotomies. In some cases, this can correct an eye position that is too wide. The third procedure, distraction osteogenesis, allows gradual shifting of the skull plates. Distraction devices designed for specific areas of the skull are surgically inserted and, just a few days after surgery, the bone plates can be moved apart by up to one millimeter each day using the built-in fixation system. The bone compensates for the gap with callus tissue, which later ossifies, creating a kind of artificial skull growth.
Outlook and prognosis
Crouzon syndrome must be treated in all cases. If no treatment of the syndrome occurs, it usually leads to death. In this case, the treatment can only be based on the symptoms of the syndrome and cannot take place causally. The malformations are corrected with the help of surgical interventions. In this case, early diagnosis and treatment have a very positive effect on the further course of the disease.Early surgery gives the brain sufficient space for healthy growth so that there are no further limitations or discomforts in the patient’s life. As a rule, the patient does not suffer from any further discomfort after the operation and there are no complications. The patient’s mental development is also not disturbed by the disease if it is treated at an early stage. Even after successful treatment, regular examinations are advisable to prevent further complaints. As a rule, Crouzon syndrome does not negatively affect the life expectancy of the affected person if it is detected early and treated completely. If Crouzon syndrome is not treated, further facial deformities will occur, which will limit the life of the affected person. Here, the shoulder joints and the eyes are particularly affected.
Prevention
Since the occurrence of Crouzon syndrome is genetic, directly preventive measures are not known. No measures exist to prevent the disease itself. Nevertheless, if the causative genetic defect is suspected, preventive measures are important to minimize the effects of the disease – especially during the growth phase. The preventive measures consist of regular visual inspection of the cranial vault and checking of intracranial pressure to allow the brain to grow normally below the cranial vault, possibly by means of surgical intervention on the cranial vault.
Follow-up
In Crouzon syndrome, no special measures of aftercare are available to the affected person in most cases. In this disease, the patient is primarily dependent on a rapid diagnosis with subsequent treatment, as this is the only way to avoid further complications or a further worsening of symptoms. A doctor should therefore be consulted at the very first signs of the disease. The earlier treatment begins, the better the further course of this disease usually is. Since this is a genetic disease, genetic counseling should always be done first if the patient wishes to have children. In this way, a recurrence of Crouzon syndrome in the descendants can be avoided. In this case, the treatment is carried out by means of a surgical intervention. The affected person should in any case rest and take care of his body after this operation. Efforts or stressful and physical activities should be refrained from in order not to strain the body unnecessarily. Furthermore, the support of one’s own family or friends and acquaintances is often very important. In most cases, the life expectancy of the affected person is not reduced by this disease.
What you can do yourself
When a child is born with Crouzon syndrome, the parents are first in line. It is important that the patient undergo extensive diagnostic testing. In this way, treatment plans can be made that include surgical procedures as well as the choice of medical aids. Skull surgery in particular must be performed as early as possible. Patients with Crouzon syndrome, however, not only require extensive medical treatment. They are usually stared at, ostracized or bullied from an early age. Here, an empathetic psychotherapy can help, in which the parents and siblings should also be included. It is often helpful for the parents and the patients to come into contact with other people affected. There are several ways to do this. For example, the website of the “Elterninitiative Apert-Syndrom und verwandte Fehlbildungen e.V.. (www.apert-syndrom.de) also provides information about Crouzon syndrome and also offers an annual educational event as a family meeting. Currently, about eighty patients with Crouzon syndrome are registered on the website “Diseasemaps”. If one joins this – reputable – site, one can get in touch with the individual patients in the respective countries (www.diseasemaps.org/de/crouzon-syndrome). Because the syndrome is inherited in an autosomal dominant manner, patients with Crouzon syndrome should seek genetic counseling if they wish to have children.
