DOOR syndrome is understood by the medical profession to be one of the rarest hereditary disorders in the world. To date, only 50 cases have been documented of the syndrome, which appears to have a genetic basis and autosomal recessive inheritance. At the current time, treatment of the deformities and retardation is symptomatic.
What is DOOR syndrome?
DOOR syndrome is an inherited disorder with a low prevalence. The name DOOR syndrome is an acronym that refers to the characteristic symptoms of the disease. The D stands for deafness and thus deafness. O in the acronym stands for osteodystrophy, meaning bone deformities. The second O stands for onychdystrophy and thus nail dystrophy. The R refers to the last leading symptom of retardation. Since therapy-resistant epilepsy also characterizes the syndrome, it is sometimes referred to as DOORS syndrome. The S stands for seizures, which means epileptic seizures. The first description took place in 1970. The French geneticist R. Walbaum is considered the first describer. Cantwell coined the DOOR term about five years later. As a hereditary disease, the syndrome has a hereditary basis. To date, only 50 cases have been documented since the initial description.
Causes
The 50 documented cases of DOOR syndrome suggest a hereditary basis, as they are indicative of familial clustering. Consequently, DOOR syndrome has been observed particularly frequently in siblings and otherwise blood relatives. Inheritance seems most likely to be autosomal recessive. Due to the small number of documented cases, the cause has not been conclusively determined and remains a subject of speculation. Many scientists assume a metabolic background. Thus, an increased concentration of 2-oxoglutaric acid has been detected in the urine and blood of affected individuals. In addition, a reduced activity of 2-oxoglutaric acid dehydrogenase has now been demonstrated. This enzyme plays a key role in energy metabolism in particular. Biosynthesis is also dependent on the enzyme. The exact cause of the reduced activity could be a genetic mutation.
Symptoms, complaints, and signs
Patients with DOOR syndrome suffer from additional optional symptoms besides those that give the syndrome its name. For example, the mothers of affected individuals often suffer from polyhydramnios, or increased amniotic fluid, during pregnancy. The patients themselves may suffer concomitant symptoms of abnormal facial features, such as an extremely large nose. Detectable changes in the organs may also be present. Finger-like altered thumbs are also frequently found on affected individuals. The same applies to various visual impairments and peripheral neuropathy. The latter symptom summarizes any disorders of the afferent nerve conductions in the peripheral nervous system. Many of the patients also suffer from analgesia and are therefore completely insensitive to pain. The individual symptoms vary in severity from case to case. If there is concomitant epilepsy, it is usually the treatment-resistant form of the disease. Many more concomitant symptoms are probably conceivable but have not been recorded to date because of the small number of cases.
Diagnosis and course
The physician makes the diagnosis on DOOR syndrome solely on the basis of clinical features. In particular, the compelling features of hearing loss, bone deformities, nail dystrophy, and retardation tempt him to make the diagnosis. The clinical picture is relatively characteristic and therefore usually does not require elaborate differential diagnosis. Only Feinmesser and Zelig described an autosomal recessive syndrome with similar symptoms in 1961. Only the mental retardation is missing in this syndrome, so that the DOOR syndrome can also be distinguished from it by a proof of the acronymically mentioned symptoms. The physician uses X-ray imaging to detect the bone deformities. The prognosis of patients varies greatly. Life expectancy may be limited to infancy, but may just as well remain relatively unrestricted. Organic manifestations in particular have an unfavorable impact on prognosis. Treatment-resistant epilepsy may also adversely affect prognosis in individual cases.
Complications
DOOR syndrome presents with many different complications that cannot be predicted.This is mainly due to the fact that DOOR syndrome is one of the rarest diseases in the world. In most cases, however, there is mental retardation. The affected person cannot think and speak clearly. Also, thought processes are not comprehensible, so that a spiritual disability occurs. This has a negative effect on the patient’s life and daily routine and can lead to depression. These symptoms are also aggravated by hearing loss, which also makes everyday life more difficult. Most patients are dependent on the help of other people. DOOR syndrome can lead to unusual facial features, which is why children in particular are teased and bullied. Psychological complaints also occur in this case. Unfortunately, there is currently no treatment for DOOR syndrome. However, the symptoms can be treated so that, for example, the abnormal facial features can be operated on. Appropriate medication can be used for epileptic seizures. If DOOR syndrome causes malformations of the organs, transplants can be performed. Whether there are complications depends largely on the treatment method. However, the affected person must live with DOOR syndrome throughout his or her life.
When should you see a doctor?
As a rule, only symptomatic treatment is possible for DOOR syndrome. For this reason, the doctor should always be consulted when the affected person suffers from symptoms due to DOOR syndrome, which in most cases are already congenital. In this case, the children suffer from significant visual disturbances and possibly also from damage to their hearing. In order to guarantee a normal development of the child, these limitations should be corrected at an early age. A doctor should always be consulted in case of other paralysis symptoms as well. Various malformations or deformities should also be examined. These can then be treated by surgery in many cases. Since the symptoms themselves can vary greatly, children in particular should attend regular medical examinations. As a rule, the diagnosis of DOOR syndrome can be made by a pediatrician or by a general practitioner. Furthermore, certain examinations that could indicate DOOR syndrome are also possible during pregnancy. However, it is not possible to prevent DOOR syndrome.
Treatment and therapy
Because only 50 cases of DOOR syndrome have been documented to date and the syndrome is one of the rarest diseases ever, research into appropriate treatment options is still in its infancy. It is also problematic that the primary cause of the complex of symptoms has not yet been determined. Since no cause has been determined, no causal treatment can exist. For these reasons, the syndrome is currently considered an incurable hereditary disease and is treated exclusively symptomatically. Hearing loss can be compensated with implants in some cases. Some bone deformities can be treated surgically. A number of antiepileptic drugs are available for epileptic seizures. However, most patients have little to no response to conservative therapy with these medications. Organic malformations must be treated surgically and may require transplantation if severe. Mental retardation can be counteracted by early intervention. Enzymatic activity can be influenced by the administration of the enzyme. However, whether this approach promises success for patients with DOOR syndrome remains a largely unanswered question and cannot be readily answered on the basis of the limited case documentation. If a genetic mutation is identified as the cause of the syndrome in the future and gene therapy approaches reach the clinical phase by then, gene therapy may be able to treat the disease causally and thus cure it.
Prospects and prognosis
DOOR syndrome can only be treated symptomatically because it is a genetic disorder. Therefore, causal therapy is not possible. If treatment does not occur, affected individuals will suffer from significant visual complaints and various malformations throughout the body. The deformities can be very different and restrict the patient’s everyday life in any case.Similarly, patients cannot feel pain, which can lead to severe injuries or misjudgement of danger. Furthermore, some nerve tracts are damaged, so that disturbances of sensitivity may occur. Due to the symptoms, the child’s development is also considerably delayed and restricted. Since treatment can only be symptomatic, only the individual symptoms are alleviated. With the help of medication, the epileptic seizures can be suppressed. Various malformations require surgical intervention in the process. The visual complaints can also be alleviated in the process, so that complete blindness can be avoided. This also increases the life expectancy of the patient. In many cases, those affected and their relatives or parents are dependent on additional psychological treatment, as it is not uncommon for depression and other psychological upsets to occur.
Prevention
Because the causes of DOOR syndrome are not definitively known, the complex of symptoms cannot yet be prevented. Genetic counseling during family planning may still be useful in families with a known case of the syndrome.
Follow-up
In DOOR syndrome, there are usually no measures of aftercare available to the affected person, so the patient is always dependent on medical treatment for this. Since this is a hereditary disease, it cannot be completely cured, so the affected person is usually dependent on lifelong therapy. If a person wishes to have children, genetic counseling can also be performed to prevent the recurrence of this disease. The earlier a doctor is consulted, the better the further course of the disease usually is. DOOR syndrome is treated by taking medication. Those affected should always ensure that the correct dosage is taken and that the medication is taken regularly so that the symptoms can be alleviated. In the event of an epileptic seizure, an emergency doctor should be called immediately or a hospital should be visited directly. Due to the disease, the affected persons are often dependent on the support of their own family or friends, whereby they also need support in their everyday life. In this context, contact with other sufferers of the syndrome can also be very useful, as this often leads to an exchange of information.
What you can do yourself
DOOR syndrome represents an extremely rare condition that, to date, cannot be treated causally. Nevertheless, there are some treatment options through which the symptoms can be alleviated. Those affected can support the medical treatment by early support and prudent behavior in everyday life. Mental retardation can be counteracted by therapeutic measures. Physiotherapy and occupational therapy as well as alternative treatment concepts have proven successful. Parents of affected children should seek information at a specialist clinic for hereditary diseases and work out an individual therapy together with the specialist. In the case of organic malformations, surgical treatment is necessary. After surgery, the patient primarily requires rest and bed rest. The doctor will also recommend a diet to promote the healing process. This usually consists of a light diet and plenty of fluids. Drinks such as alcohol, nicotine and caffeine should be avoided in the first few days after the operation. It is also important to follow the doctor’s instructions regarding wound care. The wound must be treated with special ointments so that it heals quickly and no sores are left behind.
