Sebastian Syndrome: Causes, Symptoms & Treatment

Sebastian syndrome is one of the MYH9-associated disorders and is a congenital symptom complex with the leading symptom of bleeding tendency that results from a mutation. Familial clusters have been observed. For most patients, long-term therapy is not required to lead a normal life.

What is Sebastian syndrome?

A group of congenital genetic disorders underlying a mutation of the MHY9 gene are known as MYH9-associated disorders. In addition to Fechtner syndrome, May-Hegglin anomaly, and Epstein syndrome, Sebastian syndrome also belongs to this group of diseases. This symptom complex is characterized by a bleeding tendency. The prevalence for Sebastian syndrome is low. An estimated 50 people are currently affected by the disease. The proportion of affected men and women is somewhat equal. Also, no demographic clustering has been observed to date. The first description of Sebastian syndrome took place towards the end of the 20th century. The cases documented at that time were described by Greinacher and colleagues. The low number of cases since the initial description has made research on Sebastian syndrome difficult to date. Not all of the tendencies and causes of the syndrome have been conclusively elucidated.

Causes

Sebastian syndrome does not occur sporadically but is associated with familial clustering. The 50 cases described to date have been observed in only ten different families. A genetic predisposition is suggested for this reason. Inheritance appears to be autosomal dominant. Meanwhile, a mutation has been identified as the cause of the syndrome. As in all MYH9-associated diseases, this mutation affects the MYH9 gene on gene locus q11.2 of chromosome 22. The individual diseases of the group differ only in the exact localization, but not in the type of mutation. Within the entire group, the mutations are predominantly point mutations. The different localization explains the specific symptoms of the individual syndromes. The MHY9 gene is involved in the coding of the heavy chains of non-muscle myosins type IIA. These proteins are found mainly in blood cells such as monocytes and platelets, but also in the cochlea and kidneys. As a result of the gene mutation, Sebastian syndrome patients suffer from macrothrombocytopenia, which is characterized by a deficiency of platelets and the hyperplastic size of platelets.

Symptoms, complaints, and signs

Patients with Sebastian syndrome suffer from a symptom complex of various clinical features. The most typical symptom is macrothrombocytopenia. The patients’ oversized platelets lead to platelet deficiency. In addition to the abnormal size, inclusions consisting of leukocytes are often found in the individual platelets. Platelets are instrumental in the coagulation cascade that closes wounds after injury. Due to their low platelet content, Sebastian syndrome patients suffer from bleeding tendencies because they have poorer wound closure than average. Their bleeding is markedly severe. Patients are often prone to bleeding gums or epistaxis. Women with Sebastian syndrome have significantly heavier menstrual bleeding than healthy peers. Frequent nosebleeds have also been observed in some patients. In addition, the blood loss can put a strain on the general circulatory constitution of affected individuals.

Diagnosis and course of the disease

The diagnosis of Sebastian syndrome can only be made by molecular genetic testing. Only DNA analysis can prove the association with the corresponding gene. Also, the exclusion of related syndromes can only be made by localizing the mutation during genetic analysis. The physician initiates the DNA analysis after the medical history, if the symptoms arouse in him a first suspicion of the group of MYH9-associated diseases. In principle, the prognosis is favorable for patients with Sebastian syndrome. Neither their life expectancy nor their quality of life is particularly limited by the disease. However, only slow blood clotting takes place during operations and injuries. For this reason, their risk of bleeding in accidents, for example, is higher than that of healthy persons. In the case of operations, the risk is only high if the disease was not detected beforehand.

Complications

Sebastian syndrome has a very negative impact on the quality of life of those affected and can significantly reduce it. First and foremost, the syndrome results in significantly delayed wound healing and therefore more frequent and prolonged bleeding. Especially in children, this can delay and limit development. The risk of heavy bleeding also increases during surgical procedures. Furthermore, those affected very often suffer from bleeding gums and thus possibly also from pain or inflammation. In women, Sebastian syndrome can lead to increased menstrual bleeding, which is usually associated with severe pain. Frequent nosebleeds may also occur and have a negative impact on the patient’s daily life. The frequent bleeding results in blood loss, which, if prolonged, can lead to circulatory problems. Affected individuals sometimes suffer from dizziness or fatigue. Sebastian syndrome is treated only symptomatically. As a rule, no particular complications occur. With the help of medication, the bleeding can be stopped. Life expectancy is also not limited or reduced by the syndrome in most cases.

When should you see a doctor?

A doctor must always be consulted for Sebastian syndrome. Since it is a genetic disease, there can be no self-healing, and the affected person also has only a purely symptomatic and no causal therapy available. As a rule, the doctor should be consulted in the case of Sebastian syndrome if the patient shows a strongly increased tendency to bleed. In this case, even minor injuries or minor cuts can cause very heavy bleeding, and the affected person may lose a large amount of blood. Heavy bleeding from the gums or very heavy menstrual bleeding may also indicate Sebastian syndrome and should be evaluated by a physician. If severe, an emergency physician should be called or the hospital should be visited directly to prevent further complications. Sebastian syndrome is primarily treated by the primary care physician. In case of further treatment, the affected person should always inform the doctors about the Sebastian syndrome.

Treatment and therapy

Causal therapy options are not available for patients with Sebastian syndrome, any more than they are for sufferers of the related disorders. Causal therapy would be equivalent to gene therapy. Since this treatment pathway is currently the subject of medical research, genetic disorders such as Sebastian syndrome are likely to be curable in the future. At present, however, the syndrome is still considered an incurable disease that can only be treated symptomatically. In most cases, Sebastian syndrome does not restrict the patients’ lives any further. For this reason, as a rule, no therapeutic steps are taken. This is true at least as long as those affected are not involved in accidents and have to endure just as few operations. Only in cases of severe bleeding due to serious injuries or operations does the lack of platelets have to be compensated for temporarily so that the patients do not bleed to death. Such compensation is usually achieved by administering a platelet concentrate. After administration of these concentrates, blood clotting proceeds similarly to that in healthy individuals, and the risks for any complications are thus minimized.

Prevention

Sebastian syndrome is a disease that was first documented only recently. Because only 50 cases in a total of five families have been recorded since the initial description, the research base is severely limited. For this reason, neither all factors influencing the original mutation are known, nor do preventive measures exist. Since families with cases of Sebastian syndrome have a high probability of passing on the syndrome, these families can seek molecular genetic counseling as part of family planning.

Follow-up

Sebastian syndrome is an incurable disease. As of yet, there is no way to treat it. Only symptomatic treatment can be given. In addition, there are some things that affected people should pay attention to so that they can cope with everyday life and no complications occur. It is very important that affected persons consult a doctor quickly in case of injuries. Since the blood of sufferers coagulates poorly, they must also take care in the event of accidents.Affected persons can lead a relatively normal life with appropriate therapy. Nevertheless, they should maintain contact with family and relatives very much in order to be able to call on their help and support in emergencies. For this, it is also important that the family and relatives are sufficiently informed about the disease. In emergencies, they can then act appropriately. Affected persons who suffer severely from the disease should attend permanent psychological counseling. For them, it can also be helpful to visit a self-help group. There, sufferers can talk about the disease with other sufferers and learn about other possible ways of living with the disease. Those affected then do not feel alone with the disease. Sufficient exercise and a balanced diet rich in vitamins are also very important. This reduces the risk of complications.

What you can do yourself

At the current time, Sebastian syndrome is one of the still incurable diseases. This means that there is only symptomatic therapy. For this, some everyday tips are available to minimize the health risk. Patients’ blood clots poorly, so it is very important to act quickly in the event of injury. Therefore, in case of accidents, the affected persons must pay special attention and in case of an upcoming surgery, the doctors should be informed. If there is a serious injury with heavy bleeding, a balance of platelets is required. This ensures that patients do not lose too much blood. With a platelet concentrate, the blood clotting process is similar to that of a healthy person. This reduces the risk of possible complications. Day-to-day management of the hereditary disease therefore involves certain precautions that are particularly important during sporting activities. Nevertheless, affected individuals can live relatively normal lives without long-term therapy. Inheritance of the rare disease is very likely. That is why it is advisable for those affected to have extensive family planning counseling. In this context, the main issue is molecular genetic analysis, which forms the basis for the consultation between the physician and the patient.