Nijmegen Breakage Syndrome is a rare disease that is congenital. There is a disruption in the DNA repair mechanism.
What is Nijmegen Breakage Syndrome?
Nijmegen Breakage Syndrome (NBS) is an extremely rare autosomal recessive disease. It belongs to the group of chromosomal instability syndromes and manifests itself in a variety of different symptoms. See etaizhou for What does Mediastinal Emphysema Mean.
Nijmegen Breakage Syndrome is characterized by a disruption in the DNA repair mechanism that affects all organs and cells. There is marked chromosomal fragility. The disorder in turn results in symptoms such as development and growth delays, mental development disorders, a head that is too small and immune defects.
In addition, the affected children have an increased susceptibility to serious illnesses such as lymphomas, malignant tumors and leukemia. The first description of Nijmegen breakage syndrome took place in 1981 in the Dutch city of Nijmegen (Nimwegen), from which the naming of the disease derives.
The exact frequency of Nijmegen breakage syndrome could not be determined. In the literature, 150 affected persons were described. Significantly more cases of illness are recorded in the patient registers. It is believed that the hereditary disease occurs all over the world. It is particularly common in Central and Eastern Europe among the Slavic population.
Causes
Nijmegen Breakage Syndrome is a hereditary disease. It is passed from one generation to the next in an autosomal recessive manner. The genetic cause is a mutation of the nibrin gene (NBS-1) on chromosome 8, more precisely in the q21-24 section. People who only change one gene usually do not develop diseases. On the other hand, Nijmegen breakage syndrome occurs when the affected person has two mutated nibrin genes.
A protein called nibrin is encoded by the nibrin gene. The protein is part of the protein complex that is involved in repairing DNA double-strand breaks. If the polypeptide is absent, misassembled, or damaged, the entire genetic repair mechanism is stopped.
By participating in the ATM signaling cascade, the nibrin fulfills another task. The delivery of impaired cells to apoptosis takes place. In the case of Nijmegen Breakage Syndrome, this procedure can no longer be carried out either.
Symptoms, Ailments & Signs
The symptoms that occur as part of the Nijmegen Breakage Syndrome are extremely diverse. The reason for this is that the hereditary disease affects all cells of the human body. Microcephaly is the most important symptom. The head of those affected is too small. Microcephaly is present at birth and worsens with age.
In addition, the patient has a receding chin and a receding forehead. The other facial features can vary from person to person. There are short, but also long and beak-shaped noses and eyelid gaps that run diagonally upwards. Some sufferers also suffer from choanal atresia or a cleft lip and palate.
It is not uncommon for slight growth delays and early ovarian insufficiency to occur. Around 50 percent of all patients have clinodactyly on the little fingers and syndactyly on the second and third toes. In addition, language development in children is delayed. Between 50 and 70 percent of all affected people also have vitiligo spots.
The hair of children suffering from Nijmegen breakage syndrome usually falls out sparsely and thinly. However, this finding improves with increasing age. Furthermore, congenital malformations of the kidneys are not uncommon. Additional possible symptoms include mental retardation, brain malformations such as bar hypoplasia, and various diseases of the immune system.
In addition, Nijmegen Breakage Syndrome is associated with the occurrence of malignant cancers that already appear in children and adolescents.
Diagnosis & course of disease
The Nijmegen breakage syndrome is diagnosed on the basis of the clinical symptoms, the combined immune deficiency, increased cell sensitivity to ionizing radiation and chromosome instability. In addition, the normal-length nibrin is completely absent.
Early diagnosis is considered extremely important in NBS in order not to burden the patient with unnecessary radiation or recurrent infections. Analyzing the family medical history also plays a role in the diagnosis. The doctor pays attention to possible malignant tumors, early deaths of siblings and microcephaly. The NBS diagnosis is ultimately secured with a DNA analysis.
Differential diagnoses of Bloom syndrome, NHEJ1 syndrome, Seckel syndrome, Fanconi anemia and diseases resembling Nijmegen breakage syndrome are also important. The course of the NBS usually ends badly. Only a few patients can reach adulthood. In most cases, during puberty at the latest, there is increased chromosomal fragility, which in turn leads to cancer such as lymphoma.
Corresponding treatments can only be carried out with great difficulty because radiation is not possible for the patients due to their brittleness. The use of cytostatics is therefore also considered to be problematic. X-ray examinations should generally be avoided, as the ionizing radiation increases the patient’s cancer risk.
Complications
Nijmegen Breakage Syndrome is associated with significant complications. It is a hereditary disease characterized by increased chromosomal fragility. A cure for Nijmegen Breakage Syndrome is therefore not possible. The onset of complications can only be delayed by symptomatic treatment.
It is precisely the fragility of the chromosomes that leads to malignant cancers such as leukemia, lymphomas or other malignant tumours. Due to the disturbed repair system of the DNA, the usual treatments of the cancer such as radiation or the use of cytostatics are associated with further dangers in the case of chromosome breaks. The existing cancer can be treated in this way. However, chromosomal breaks that occur as a result of radiation or drug therapy are difficult to repair.
As a result, new malignant tumors develop. For this reason alone, only a few of those affected reach adulthood. X-ray and CT examinations should also be avoided because they are associated with very high risks due to chromosomal instability. Another serious symptom of Nijmegen breakage syndrome is also the pronounced immune deficiency. This leads to numerous infectious diseases that require constant treatment.
Due to these infections, the life expectancy of the patients is also very limited. Furthermore, the mental development of the child can be severely disturbed by the malformations of the brain, so that in addition to fighting infectious diseases and cancer, constant psychological and psychotherapeutic treatment is necessary.
When should you go to the doctor?
Nijmegen Breakage Syndrome is a congenital condition diagnosed immediately after birth. Due to the various malformations and other complications, close medical treatment is necessary in every case. Parents of affected children should inform the pediatrician if any unusual symptoms or signs occur. If the child’s state of health suddenly deteriorates, medical advice is also required.
Serious complaints such as tumors or immune deficiencies must be treated as inpatients in a hospital or a specialist clinic for genetic diseases. If there are already cases of the disease in the family, a genetic test should be carried out during pregnancy.
The result provides information as to whether the child also suffers from Nijmegen breakage syndrome and thus enables early treatment. The disease can be diagnosed by a specialist doctor. The individual symptoms are examined and treated by the responsible doctors. For example, growth disorders must be presented to an orthopedist, among other things, while lymphomas and leukemias must be treated by a dermatologist.
Treatment & Therapy
Therapy of the cause of Nijmegen breakage syndrome is not possible. For this reason, treatment is limited to the symptoms. It includes physiotherapeutic applications, fighting infections and psychological care. If cancer breaks out, the usual treatment measures of cancer therapy are carried out as far as possible. Multidisciplinary treatments and long-term check-ups are also important.
Outlook & Forecast
Nijmegen breakage syndrome has an unfavorable prognosis. Patients experience health problems of organs as well as cells. Numerous symptoms in different areas occur, which lead to a great deal of stress for the affected person and their relatives. Most of the time, living independently is unthinkable.
The disease cannot be cured with the current legal and medical possibilities. There is a genetic defect that cannot be repaired. Doctors are not allowed by law to alter human genetics. The treating doctor therefore concentrates on the individually pronounced symptoms and draws up a corresponding treatment plan, which is regularly adapted over the course of life.
The aim of therapy is to improve the general quality of life and alleviate existing symptoms. A recovery from this syndrome can be ruled out to this day. Due to the large number of different complaints, it can lead to severe emotional overload. Psychological care is therefore often necessary to prevent secondary diseases that have a negative impact on further physical processes.
Since the risk of developing cancer in the patient is increased, check-ups are necessary at regular intervals. Nevertheless, even with early detection of malignant tissue changes and intensive medical care, premature death of the affected person is often the result due to the unfavorable course of the disease.
Prevention
Unfortunately, it is not possible to prevent Nijmegen Breakage Syndrome. It is one of the congenital diseases.
Aftercare
In most cases, sufferers of Nijmegen Breakage Syndrome have no specific or direct follow-up measures available. Since this is a congenital disease, it cannot be completely cured. If the patient wishes to have children, a genetic examination and counseling is recommended so that the Nijmegen breakage syndrome does not occur again in the offspring.
Most of those affected are dependent on various surgical interventions that can alleviate the symptoms and deformities. Bed rest should always be observed after such interventions, whereby the person concerned should rest in any case. Efforts or other physical activities should be avoided. In many cases it is also necessary to take various medications.
The correct dosage and regular intake is always important. If anything is unclear or you have any questions, you should always consult a doctor first. Those affected are often dependent on help and care from relatives and their own families in their everyday lives. Psychological support also has a very positive effect on the further course of the symptoms. The life expectancy of the person affected may also be reduced due to Nijmegen Breakage Syndrome.
You can do that yourself
Since Nijmegen Breakage Syndrome is a genetic disease, there is currently no causal treatment available. Therapy can only be symptomatic. It is important to respond individually to the disease status of the respective patient. In addition to medical therapies, other alternative therapy methods can be used to improve the quality of life of those affected.
Parents and relatives can help sick children through various types of stimulation to train functions that are restricted by the disease. Small individual successes can boost the patient ‘s self-esteem. Doctors and physical therapists can also provide guidance on light exercise methods designed to maintain people’s physical fitness.
In addition to appropriately demanding, mental and physical exercises, there are also various relaxation methods that parents of affected children can learn and use at home. These include, among other things, different types of meditation. Also, for example, singing bowls or dance therapy can help to challenge and promote different senses of the children. It is important to apply these measures continuously. At best, this is the only way to achieve an increase in performance in various areas of life.
In addition to centering the individual, it can be extremely important for affected children and caring relatives to also involve the social environment in non-medical measures. An intact social network helps to deal with the stress better.
