In medicine, the Crane-Heise syndrome is a complex of malformations, which mainly consist of insufficient ossification of the skull and aplasia of the vertebrae. The syndrome is due to a hereditary mutation that is based on an autosomal recessive inheritance. The prognosis is unfavorable and the course is usually fatal.
What is Crane-Heise Syndrome?
The 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 roof of the skull, multiple malformations in the area of the face and altered vertebral bodies as well as non-attached collarbones.
The syndrome was first described by Crane and Heise at the end of the 20th century. The name of the hereditary disease as Crane-Heise-Syndrome has prevailed in honor of the first description. Only nine cases of the syndrome have been documented since it was first described. Nevertheless, the research situation is well advanced.
In the meantime it has even been possible to elucidate the etiological connections between the disease. Nevertheless, the primary cause remains in the dark, as the research options are limited because of the few cases so far.
Causes
Hereditary and genetic factors are the basis of Crane-Heise syndrome. On the basis of research in the cases documented so far, the malformation complex does not appear to occur sporadically, but rather to be subject to familial accumulation. The few cases described suggest an autosomal recessive inheritance pathway for the symptom complex. A mutation seems to favor the syndrome.
In the meantime, a genetic mutation has been brought into causal connection with the symptom complex. The gene that is causally associated with the syndrome corresponds to the FGD1 gene located on an X chromosome with the gene locus p11.21. This gene is involved in the regulation of the Golgi apparatus by activating Cdc42 as a membrane component.
Symptoms, ailments & signs
The characteristic clinical symptoms of Crane-Heise syndrome are an inadequately ossified roof of the skull and retarded development, which often manifests itself as an intrauterine growth retardation. The insufficient ossification of the skullcap is related to insufficient mineralization of the skull.
The patients also have malformations in the area of the face. As such, microgenius, cleft palate and hypertelorism are particularly common. Many patients also have abnormal nostrils that point far forward. In some cases, the children’s auricles can also be affected by malformations. In all previously documented cases, there were aplasias in the area of the collarbones.
These aplasias appear as a complete non-application of the anatomical structures. In addition to these aplasias, the cervical vertebrae can also be affected by aplasias. In any case, the syndrome with its multiple malformations can be recognized immediately after birth.
Diagnosis & course
The first suspected diagnosis of Crane-Heise syndrome can be made immediately after birth using a visual and X-ray diagnosis. The imaging shows the aplasias of the collarbones. Imaging of the head can reveal insufficient ossification on the roof of the skull.
Accrued differential diagnoses are in addition to the kleidokranialen dysplasia as the Yunis-Varon syndrome that pycnodysostosis or craniosynostosis-anal anomalies-porokeratosis syndrome. A molecular genetic analysis can be carried out to confirm the diagnosis of Crane-Heise syndrome. If the first suspected diagnosis is correct, the analysis provides evidence of a mutation in the FGD1 gene on an X chromosome in the p11.21 gene locus.
In the meantime, prenatal diagnosis of Crane-Heise syndrome is also possible. The malformations on the head and on the spine can be detected by fine ultrasound. The malformation ultrasound enables the targeted search for vertebral and cerebral malformations. The prognosis for children with Crane-Heise syndrome is always poor. In almost all documented cases, the patients died a short time after birth. A fatal course is therefore likely.
Complications
The Crane-Heise syndrome causes multiple malformations of the anatomical structures, which causes high levels of suffering and serious complications for the children concerned. Characteristic symptoms are an open, insufficiently ossified skullcap and massive developmental disorders, which often manifest themselves before birth.
The malformations in the face are characterized by a rearwardly displaced lower jaw and an incorrect interpupillary distance. Malformed auricles are also not uncommon. Children with Crane-Heise syndrome therefore have visual and hearing impairments. Food intake is not possible because of the malformed lower jaw and cleft palate.
Serious disorders in the area of the anatomical structures, which occur in the form of deformed vertebral bodies and missing collarbones, prevent normal movement sequences. Due to these serious complications, promising treatment is not possible and the prognosis is negative in all cases.
The life restrictions associated with the Crane-Heise syndrome cannot be eliminated even through operations and other individual therapies. In particular, the severe cerebral malformations can hardly be corrected.
The patients show such a high level of instability that even treatment approaches to correct the fascial malformations are not effective, according to doctors. There is also no time for individual therapeutic approaches, as the children either die 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 started routinely. Further visits to the doctor are necessary if the malformations cause symptoms and complications. For example, a cleft palate can lead to problems with food intake, which must be clarified by a specialist. An audiologist should be consulted in the event of malformations of the auricles. In addition, general advice from the pediatrician is useful.
The doctor will show the parents, among other things, possibilities for psychological support and cosmetic interventions. Therapeutic advice should always be given. Should the child develop mental problems later in life, this must be clarified. If an accident or fall occurs as a result of a malformation, the emergency doctor must be consulted. Unusual symptoms are also best presented to a doctor immediately. In addition to the pediatrician or family doctor, a specialist in hereditary diseases or the emergency medical service can also be called in.
Treatment & Therapy
There is currently no causal therapy for patients with Crane-Heise syndrome. Genetic therapies are now a subject of medical research, but so far they have not been successfully established as a treatment method. Eventually, following advances in gene therapy, there will be causal treatment options for patients with Crane-Heise syndrome in the future.
With the current state of medicine, however, there is no prospect of a cure. Because of the small number of documented cases and the even smaller number of patients with a life span longer than a few hours, symptomatic treatment options for Crane-Heise syndrome are also hardly recorded. 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 Crane-Heise syndrome, they are not expedient and would probably end fatally. For this reason, the focus of treatment is on improving the quality of life in an 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, psychotherapy prepares the parents for the child’s birth and the presumably immediate postnatal death of the child. In the best case scenario, the therapy continues after the birth and infant death and helps the family to come to terms with what they have experienced. In addition, since the syndrome is a hereditary condition, parents need to be educated about the risks to future children.
Outlook & forecast
In most cases, the affected person dies from Crane-Heise syndrome. Since the syndrome is caused by a genetic defect, it cannot be treated causally, but only symptomatically.
The patients suffer from severe delays in growth and development. A cleft palate forms, whereby the ears can also be affected by malformations. The malformations themselves can be treated with surgical interventions. However, it is not possible to treat the instability of the skull in a way that the person can survive.
For this reason, the Crane-Heise syndrome always leads to a significantly reduced life expectancy for the patient. Furthermore, the parents and relatives often suffer from the consequences of the syndrome and show depression or other psychological disorders.
As it is a genetic disease, parents need genetic counseling to prevent Crane-Heise syndrome from occurring in future generations. If the syndrome is diagnosed before birth, an abortion can also be done if the parents decide against the child.
Prevention
The Crane-Heise syndrome cannot yet be prevented. This is mainly due to the fact that medicine has not yet identified the actual cause of the mutation in the causative gene. In the case of a prenatal diagnosis, the parents can decide against the child if necessary.
Aftercare
In the case of Crane-Heise syndrome, there are usually no direct follow-up options available to the patient. The person concerned must first and foremost consult a doctor early on so that there are no further complications or complaints. An early detection of the disease always has a very positive effect on the further course and can limit further complaints or complications.
Since this is a hereditary disease, genetic counseling should be carried out if you want to have children in order to prevent the recurrence of Crane-Heise syndrome. The treatment itself takes place with the help of surgical interventions that are intended to correct the malformations. After such procedures, the person concerned should definitely rest and not engage in stressful or physical activities.
Most of the patients are also dependent on the help and care of their parents or friends in their everyday life, whereby this care can also prevent depression or other psychological upsets. If the child dies prematurely as a result of the Crane-Heise syndrome, the parents and relatives are dependent on intensive psychological therapy in order to deal with the death properly.
You can do that yourself
Crane-Heise syndrome is a serious disease that is almost always fatal. Parents of affected children are therefore under great emotional stress. Discussions with a therapist and a visit to a self-help group are the first steps to help overcome the trauma.
If the outcome 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, additional measures must be taken.
Any facial malformations require surgical removal, which must be prepared accordingly. Aplasias and growth disorders of the bones are also clinical symptoms that must be treated surgically. The necessary measures can be determined by talking to the doctor.
Parents who feel overwhelmed by the child’s illness 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 space for healthy interaction with the child. During the course of the illness, regular doctor’s discussions apply so that the therapy can always be individually adapted to the child’s state of health.
