Muenke syndrome is characterized conductively by craniosyostosis of the coronary suture due to a mutation in the FGFR3 gene. The disease is inherited in an autosomal dominant manner and is often accompanied symptomatically by abnormal extremities. Treatment usually corresponds to surgical intervention.
What is Muenke syndrome?
In craniosynostosis, one or more cranial sutures ossify prematurely during embryonic development, preventing physiologic growth of the skull and brain. Many diseases in the group of congenital malformation syndromes with predominant involvement of the face include such craniosyostoses. One such disease is coronal suture synostosis syndrome, also known as Muenke syndrome. The disease was first described in 1997, and M. Muenke and colleagues are considered to be the first describers. Muenke syndrome is characterized by craniosynostosis of the coronal suture and includes additional skeletal changes of the tarsal and carpal bones. The prevalence of the syndrome is unknown to date. Manifestation occurs in the early neonatal period or at the latest in early infancy. Although the condition has not been conclusively studied, the cause has now been elucidated.
Causes
Muenke syndrome has been associated with familial clustering in many cases. In these cases, the mode of inheritance most closely corresponds to an autosomal dominant mode of inheritance. However, cases have also been documented in which the syndrome appears to be sporadic. The cause appears to be a genetic mutation, which in the sporadic cases probably corresponds to a new mutation. The location of the mutation is also thought to have been identified. In particular, the disease is thought to be caused by mutations in the FGFR3 gene, which is located at gene locus 4p16.3. Other syndromes have also been linked to the FGFR3 gene. One example is the so-called Apert syndrome. The gene encodes within the DNA for fibroblast growth factor receptor 3. Little is known about the physiological effects of FGF-3 growth factor. Speculation suggests that FGF-3 is a critical factor, particularly for embryonic development. Mutation of the receptors probably results in inadequate binding of the growth factor during embryonic development.
Symptoms, complaints, and signs
Patients with Muenke syndrome suffer from a variety of symptoms. Because of premature closure of their coronal suture, affected individuals have an abnormal head shape, which also manifests in facial abnormalities. In addition to a shortened anterio-posterior skull diameter, there are usually diminished orbital depths. Often these symptoms are associated with hypoplasia of the maxilla. When there is unilateral closure of the coronal suture, the orbits are flattened on the corresponding side. Usually, the patients’ intelligence is not affected by the syndrome. On the limbs, fusions of hand bones or tarsal bones are found. Malsegregation is also conceivable at the carpal bones. In addition, cone epiphyses are among the possible symptoms. In some cases, the clinical picture of patients is additionally associated with osteochondromas. Phenotypic and thus symptomatic overlap with other syndromes such as Pfeiffer syndrome, Jackson-Weiss syndrome, or Saethre-Chotzen syndrome are clinically conceivable manifestations.
Diagnosis and disease course
The diagnosis of Muenke syndrome is usually made in the neonatal period because the disease can be identified early by visual diagnosis. Approximately one patient in 15,000 newborns suffers from synostosis of the coronal suture. However, this phenomenon does not automatically have to be due to Muenke syndrome. Therefore, the diagnosis requires the detection of the pathogenic mutation in the FGFR3 gene. Patients’ hands and feet may appear normal radiographically, so looking for abnormalities in this regard is not sufficient for diagnosis. In principle, all children with cranial suture synostosis can be screened for the specific P250R mutation. This examination corresponds to a molecular genetic analysis. Exclusion of the mutation does not necessarily mean that the patient does not have Muenke syndrome. In a few cases, the mutation could not be detected in affected individuals. However, detection is considered diagnostic. Female patients have a less favorable prognosis.
Complications
As a result of Muenke syndrome, affected individuals suffer from various malformations and deformities, mainly on the patient’s head and face. Due to these malformations, it is not uncommon for patients to experience psychological symptoms and depression. Those affected often suffer from inferiority complexes and reduced self-esteem. There are often feelings of shame due to the complaints and especially children can be affected by bullying and teasing due to Muenke syndrome. However, intelligence is not impaired, so the mental development of patients progresses without complications. Similarly, there are deformities of the limbs, so that in everyday life there may be restrictions in various activities or limited movement. The quality of life is significantly reduced by Muenke syndrome. Treatment of Muenke syndrome does not lead to further complications. As a rule, no causal treatment is possible, but some surgical interventions must be performed to prevent further consequential damage. The life expectancy of the affected person is usually not limited. Treatment can also take place directly after birth. In some cases, the parents of the children are also affected by psychological symptoms due to Muenke syndrome.
When should you see a doctor?
The characteristic deformities of the head and face are clear indications of Muenke syndrome and usually lead to a diagnosis immediately after birth. If the symptoms are mild, the doctor in charge should be informed of any symptoms. For example, there may be isolated cases of fused wrist or tarsal bones, resulting in the gait typical of the disease. Persons who already have a family history of the disease should arrange for a genetic test at an early stage. Then the necessary treatment steps can be initiated immediately after birth. Parents of affected children should also inform the family doctor of any new symptoms that arise and of any other deviating behavior on the part of the child. In addition, close monitoring by a specialist is always necessary. In most cases, treatment takes place in a hospital or in a specialized clinic for genetic diseases. In addition to the general practitioner, the orthopedist or an internist may be consulted. In the case of chronic complaints, therapy and physiotherapy are also part of the treatment.
Treatment and therapy
Causal treatment is not available for patients with Muenke syndrome. Gene therapy approaches offer hope for causal therapy, but these have not currently reached the clinical phase. Treatment is purely symptomatic and thus depends on the symptoms in each individual case. Only surgical treatment approaches can be considered to correct the cranial anomalies. The surgical procedure is designed to help relieve the pressure on the brain caused by early closure of the cranial suture. In this way, the cranial nerves are relieved of pressure and, ideally, are less compressed or not compressed at all after surgery. For less severe craniosynostosis, a conservative treatment option is available. For example, more mildly affected children may receive skull molds that they must wear long-term. These skull molds attempt to adequately reshape the skull. Since Muenke syndrome is usually diagnosed in the neonatal period, such conservative remodeling is particularly suitable: the head shape of infants is still adaptable. Conservative remodeling ultimately has the same goal as surgical modeling. Physiological brain growth should be enabled by the treatment. In addition, the appearance of the head is brought into line with the average. Accompanying symptoms such as the deformities of the extremities can be treated surgically. If they do not limit or disable the affected person, such treatment is not mandatory.
Outlook and prognosis
Muenke syndrome is a rare condition, but it can now be well treated surgically. If premature closure of the coronary suture is detected in time, the prognosis is good. Any malformations can be treated surgically. Appropriate medications can be prescribed for symptoms such as pain or sensory disturbances. Life expectancy is not reduced by coronary suture synostosis syndrome.The quality of life may be slightly limited due to mentioned discomfort as well as possible scars in the area of the face and head. In general, however, the prognosis is positive. Children suffering from Muenke syndrome are particularly susceptible to sensorineural hearing loss. Poor hearing can lead to problems, especially later in life, when, for example, the patient is no longer able to understand instructions or navigate everyday life. Due to exclusion and reduced self-esteem, some of those with the disease develop psychological complaints. Well-being can be lowered if the sufferer does not have a good support network in the form of parents, relatives, friends and therapists. In any case, children suffering from Muenke syndrome need support in everyday life in order to remain mentally and physically healthy despite the disease.
Prevention
Muenke syndrome cannot be prevented because it is influenced by genetic factors instead of external ones. The only preventive measure is genetic counseling during pregnancy.
Follow-up
In most cases of Muenke syndrome, only very few and also very limited measures of direct aftercare are available to affected individuals. First and foremost, a rapid and, above all, an early diagnosis of this disease should be made so that no further complications can occur. Since Muenke syndrome is a genetic disease, it cannot be completely cured. However, in the case of those who wish to have children, genetic testing and counseling may be useful to prevent the recurrence of the syndrome. Most of the affected persons have to undergo a surgical intervention. In any case, the patient should rest and take it easy after such an operation, ideally keeping to bed rest. Likewise, strenuous or physical activities should be avoided in order not to put unnecessary strain on the body. In many cases, those affected by the syndrome are also dependent on help and support from their own family in everyday life. In this context, loving and intensive conversations with one’s own family and friends also have a very positive effect on the further course of the disease. Not infrequently, the development of depression or other psychological upsets can be prevented in this way.
What you can do yourself
Muenke syndrome is usually treated surgically and with medication. The most important self-help measure is to take it easy on the body after the procedure and to consult closely with the doctor in charge. Parents of affected children should keep a close eye on the child and inform the responsible physician of any abnormalities. In general, Muenke syndrome can be treated relatively well and does not result in permanent limitations in the quality of life. However, deformities and malformations almost always remain, which can sometimes be a great psychological burden for those affected. For this reason, medical treatment should be supported by therapeutic measures. Severely affected children with developmental discrepancies used to be advised to attend a special kindergarten and later a special school. Today, reference is instead made to inclusion at regular schools. Children without further abnormalities can attend normal and higher schools anyway. Especially in the case of severe movement impairments, comprehensive therapy is necessary. Parents can support these measures by encouraging the child in everyday life. In most cases, further physiotherapeutic measures are also indicated. Since the disease can also place a considerable burden on family members, parents and friends should also seek therapeutic help. The therapist can also establish contact with other sufferers and refer the parents to a self-help group if necessary.
