Crane-Heise syndrome is the medical term for a complex of malformations consisting mainly of insufficient ossification of the skull and aplasia of the vertebrae. The syndrome is due to a hereditary mutation, which is based on an autosomal recessive inheritance. The prognosis is unfavorable and the course is usually lethal.
What is Crane-Heise syndrome?
Crane-Heise syndrome is a symptom complex from the group of hereditary diseases. The syndrome is characterized by a complex of clinical symptoms such as inadequate ossification on the skull roof, multiple malformations in the facial region, and altered vertebral bodies and nonunion of the clavicles. The syndrome was first described by Crane and Heise in the late 20th century. The name of the hereditary disease as Crane-Heise syndrome has become accepted in honor of the first descriptors. Since the initial description, a total of only nine cases of the syndrome have been documented. Nevertheless, the research situation is far advanced. In the meantime, even etiological correlations of the disease could be elucidated. Nevertheless, the primary cause remains obscure so far, as research options are limited due to the small number of cases so far.
Causes
Hereditary and genetic factors underlie Crane-Heise syndrome. On the research basis of the cases documented to date, the malformation complex does not appear to occur sporadically but is subject to familial clustering. The few cases described suggest autosomal recessive inheritance as the mode of transmission of the symptom complex. A mutation seems to favor the syndrome. Meanwhile, a genetic mutation has been causally linked to the symptom complex. The gene causally associated with the syndrome corresponds to the gene FGD1 located on an X chromosome with gene locus p11.21. This gene is involved in the regulation of the Golgi apparatus by activating Cdc42 as a membrane component.
Symptoms, complaints, and signs
The characteristic clinical symptoms of Crane-Heise syndrome are an inadequately ossified skull roof and retarded development, which often manifests as intrauterine growth retardation. Insufficient ossification of the cranial calvaria is related to insufficient mineralization of the skull. Patients additionally show malformations in the facial region. As such, microgenia, cleft palate, and hypertelorism are most common. Many patients also have abnormal nostrils that point far forward. In some cases, the auricles of the children may also be affected by malformations. In all cases documented to date, aplasias were present in the clavicle region. These aplasias appear as complete nonunion of the anatomic structures. In addition to these aplasias, the cervical vertebrae may also be affected by aplasias. In any case, the syndrome with its multiple malformations can be recognized immediately after birth.
Diagnosis and course
The first suspected diagnosis of Crane-Heise syndrome can be made immediately after birth by means of visual and radiographic diagnosis. Imaging reveals aplasia of the clavicles. Imaging of the head may reveal inadequate ossification at the cranial vault. Differential diagnoses to be distinguished include Yunis-Varon syndrome, pycnodysostosis, or CDAGS syndrome in addition to kleidocranial dysplasia. To confirm the diagnosis of Crane-Heise syndrome, molecular genetic analysis can be performed. If the first suspected diagnosis is correct, the analysis provides evidence of a mutation of the FGD1 gene on an X chromosome in gene locus p11.21. Meanwhile, prenatal diagnosis of Crane-Heise syndrome is also possible. The malformations of the head and spine can be detected by fine ultrasound. Malformation ultrasound allows a targeted search for vertebral and cerebral malformations. The prognosis for children with Crane-Heise syndrome is always unfavorable. In almost all documented cases, the patients died a short time after birth. A lethal course is therefore likely.
Complications
Crane-Heise syndrome causes multiple malformations of anatomic structures, resulting in high distress and severe complications in affected children.Characteristic symptoms are an open, insufficiently ossified skull and massive developmental disorders, which often manifest themselves before birth. The facial malformations are characterized by a displaced lower jaw and defective eye spacing. Malformed auricles are also not uncommon. Children with Crane-Heise syndrome therefore show visual and hearing disorders. Food intake is not possible due to the malformed lower jaw and cleft palate. Severe disturbances in the anatomical structures, which take the form of deformed vertebral bodies and missing clavicles, prevent normal movement. Due to these serious complications, promising treatment is not possible and the prognosis is negative in all cases. The life restrictions associated with Crane-Heise syndrome cannot be eliminated even by surgery and further individual therapies. Especially the severe cerebral malformations are hardly correctable. The patients show such a high degree of instability that even treatment approaches to correct the fascial malformations are not effective, according to medical experts. There is also no time left for individual therapy approaches, as the children die either immediately after birth or a few hours later.
When should you go to the doctor?
Crane-Heise syndrome is usually diagnosed immediately after birth, and treatment is routinely initiated. Further visits to the doctor are required if symptoms and complications develop as a result of the malformations. For example, as a result of a cleft palate, there may be problems with feeding, which must be clarified by a specialist. In the case of malformations of the auricles, an ear specialist should be consulted. Accompanying this, a general consultation with a pediatrician is useful. Among other things, the physician will show the parents possibilities for psychological support and cosmetic interventions. Therapeutic counseling should be provided in any case. If the child develops psychological problems later in life, it is essential that this be clarified. If an accident or fall occurs as a result of a deformity, the emergency physician must be consulted. Unusual symptoms are also best presented to a doctor immediately. In addition to the pediatrician or family doctor, a specialist for hereditary diseases or directly the medical emergency service can be called in.
Treatment and therapy
A causal therapy does not yet exist for patients with Crane-Heise syndrome. Although genetic therapies are now a subject of medical research, they have not yet been successfully established as a treatment method. Possibly in the future, following advances in gene therapy, causal treatment pathways for patients with Crane-Heise syndrome will become available. However, with the current state of medicine, there is no cure in sight. Because of the small number of documented cases and the even smaller number of patients with a lifespan longer than a few hours, symptomatic treatment options for Crane-Heise syndrome are also poorly understood. Especially the cerebral malformations can hardly be corrected. Corrections of the fascial malformations would be conceivable, but in view of the instability of patients with the Crane-Heise-Syndrome they are not target-oriented and would probably end lethally. For this reason, the focus of treatment is on improving the quality of life of the already short life. One of the most important therapy steps is the psychotherapeutic care of the parents. If the syndrome has already been diagnosed prenatally, the parents are prepared in psychotherapy for the birth and the death of the child, which probably occurs immediately postnatally. After the birth and the child’s death, the therapy continues in the best case and helps the family to come to terms with what they have experienced. In addition, because the syndrome is a hereditary disease, parents must be educated about the risks to future children.
Outlook and prognosis
In most cases, Crane-Heise syndrome causes the death of the affected person. Because the syndrome results from a genetic defect, it also cannot be treated causally, only symptomatically. The patients suffer from severe delays in growth and also in development. A cleft palate develops, and the ears may also be affected by malformations.The deformities themselves can be treated by surgical intervention. However, it is not possible to treat the instability of the skull in such a way that the affected person can survive. For this reason, Crane-Heise syndrome always leads to a significantly reduced life expectancy of the patient. Furthermore, parents and relatives often also suffer from the consequences of the syndrome, showing depression or other psychological upsets. Since it is a genetic disease, parents are dependent on genetic counseling to prevent the occurrence of Crane-Heise syndrome in the next generations. If the syndrome is diagnosed before birth, abortion may also occur if the parents decide not to have the child.
Prevention
So far, Crane-Heise syndrome cannot be prevented. This is mainly because medical science has not yet identified the actual cause of the mutation in the gene that causes it. If prenatal diagnostics are performed, parents may decide not to have the child.
Follow-up
In Crane-Heise syndrome, there are usually no direct options for follow-up care available to the patient. In this case, the affected person must primarily see a doctor at an early stage to prevent further complications or discomfort. Early detection of the disease always has a very positive effect on the further course of the disease and can limit further complaints or complications. Since this is a hereditary disease, genetic counseling should be performed if the patient wishes to have children in order to prevent the recurrence of Crane-Heise syndrome. The treatment itself involves surgical interventions to correct the deformities. After such operations, the affected person should rest in any case and not perform any stressful or physical activities. Most patients also depend on the help and care of their parents or friends in their daily lives, and this care can also prevent depression or other psychological upsets. If Crane-Heise syndrome causes the child to die prematurely, the parents and family members depend on intensive psychological therapy to properly cope with the death.
Here’s what you can do yourself
Crane-Heise syndrome is a serious condition that is almost always fatal. Parents of affected children are under great emotional stress as a result. Talking to a therapist and attending a support group are initial measures that help overcome the trauma. If the course is positive, the child will need permanent care. This can also be an enormous burden for the parents, which is why the help of an outpatient care service is necessary in this case. Depending on the severity of the Crane-Heise syndrome, further measures must be taken. For example, any facial malformations require surgical removal, which must be prepared accordingly. Aplasias and growth disorders of the bones are also clinical manifestations that must be treated surgically. The necessary measures can be determined in discussion with the physician. Parents who feel overwhelmed by the child’s disease should seek professional help at an early stage. Patients with Crane-Heise syndrome can be treated in special clinics. This makes everyday life easier for the parents and offers scope for healthy interaction with the child. In the course of the disease, regular medical consultations apply so that the therapy can always be individually adapted to the child’s state of health.
