Epstein Syndrome: Causes, Symptoms & Treatment

Epstein syndrome is the most severe form of MHY9-associated disease and, like all syndromes in the group, is caused by mutations in the MHY9 gene and is inherited in an autosomal dominant manner. The syndrome manifests as platelet deficiency, hearing loss, and inflammation of the kidneys. Treatment is symptomatic.

What is Epstein syndrome?

The disease group of thrombocytopenias caused by MYH9 gene mutation is also known as the MYH9-associated group. These are rare inherited disorders that include Sebastian syndrome, May-Hegglin anomaly, and Fechtner syndromes, as well as the so-called Epstein syndrome. Due to its rarity, no reliable data on the epidemiology or the exact prevalence of the symptom complex exist so far. For MYH9-associated diseases, research so far assumes a frequency of between one and nine cases in 1000000 people. This would put the prevalence for Epstein syndrome as a single disease well below 1:1000,000. Epstein syndrome has been described in fewer than 100 familial cases since it was first described. In the late 20th century, it was Charles J. Epstein who first described the syndrome and bequeathed it the name. Epstein syndrome is also called nephrotic syndrome because it manifests not only in the platelets but also in the kidneys.

Causes

Like all MYH9-associated disorders, Epstein syndrome does not appear to occur sporadically. A familial cluster was observed in the 100 documented cases. Apparently, an autosomal dominant inheritance underlies the symptom complex. The MYH9-associated diseases are caused by a mutation in the MHY9 gene. Depending on the individual disease, the exact location of the mutation differs, so that different symptoms characterize the individual diseases of the group. In Epstein syndrome, point mutations of the MYH9 gene are present, affecting chromosome 22 in gene locus q11.2. The MHY9 gene encodes heavy chains of NMMHC-IIA, the so-called non-muscle myosin. This is a protein in blood cells such as monocytes and platelets, in the cochlea and kidneys. The Epstein syndrome mutation alters the conformation in the head portion of the protein and interferes with aggregation to form the Doehle bodies. In this way, an abnormal cytoskeleton is formed for megakaryocytes, which are the precursors of platelets.

Symptoms, complaints, and signs

Patients of Epstein syndrome suffer from a complex of clinical symptoms. One of the most important symptoms is the characteristic lack of platelets, called thrombocytopenia. In addition, there is a functional disorder also known as thrombocytopathy. The few platelets in the patient’s blood are markedly enlarged. This macrothrombocytopenia is not associated with leukocyte inclusion in Epstein syndrome, unlike other syndromes in the group. Because the mutant protein from the MHY9 gene is also present in the cochlea, some patients with Epstein syndrome develop hearing loss that progresses in a progressive manner. The hearing loss mainly affects the high frequency range. In addition to these manifestations, in most cases there is a manifestation in the kidneys. This is usually glomerulonephritis associated with inflammation of the renal filters. However, the symptoms of the kidneys and ears do not necessarily occur. If the impaired aggregation of NMMHC-IIA protein is compensated with the help of another myosin form, the symptoms of thrombocytopathy and macrothrombocytopenia mentioned first will remain.

Diagnosis

Epstein syndrome is a congenital disorder. Therefore, the platelet changes manifest immediately after birth. However, because these changes are not directly visible, the diagnosis is usually made late. Often, only renal symptoms or progressive hearing loss lead to a detailed diagnosis. Histologically, the shape-altered platelets are conspicuous. Platelet deficiency is also an important criterion for diagnosis. Differentiation from other syndromes of the group occurs at the latest with renal symptoms. The lack of leukocyte inclusions also differentiates Epstein syndrome from other MHY9-associated disorders. To confirm a suspected diagnosis, molecular genetic analysis can be used to provide evidence of the genetic mutation.Epstein syndrome is sometimes the most serious syndrome in the group of MHY9-associated diseases.

Complications

Because of Epstein syndrome, in most cases the patient suffers from very serious complications. Usually, there is complete hearing loss and inflammation of the kidneys. Due to the hearing loss, the affected person is severely restricted in his or her everyday life. Especially in young people, this can lead to severe psychological problems. The hearing loss does not have to occur suddenly, but it can increase as the disease progresses. Treatment can only target the symptoms that occur, but it is not possible to cure Epstein’s syndrome completely. The hearing loss can be compensated by hearing aids. This is usually only possible if there is not a complete loss of hearing. If the hearing loss remains at a certain level, implants can also be placed in the ear. In this case, there are no complications. Complications can occur with bleeding and surgery and are therefore treated with platelet concentrates. If infections or inflammations of the kidneys occur, they can also be treated with medication. However, the patient must live with the syndrome his or her entire life.

When should one go to the doctor?

If the affected person suffers from changes in the usual hearing ability, there is reason for concern. A doctor should be consulted, as progressive hearing loss may develop without treatment. Hearing problems occur particularly in the frequency range of higher tones and should be examined by a physician. Disorders of kidney function should also be presented to a physician and treated by him. If stabbing or pulling pain occurs in the region of the kidneys, a physician is needed. If there are changes in the urine or problems with urination, these signs should be discussed with a doctor. If the symptoms spread or increase in intensity, a doctor should be consulted as soon as possible. If the affected person suffers from sudden and incomprehensible nosebleeds or bleeding gums, a doctor should be consulted. If bleeding is difficult to stop after minor to moderate cuts, a doctor should be consulted. If heart palpitations, high blood pressure, dizziness or general weakness occur due to excessive blood loss, it is necessary to consult a doctor. In case of sleep disturbances, increased stress, inner malaise or a diffuse feeling of illness, a doctor should be consulted. If the symptoms persist for several days or weeks, medical care is needed.

Treatment and therapy

To treat Epstein syndrome causally, gene therapy would be needed. These treatment interventions are currently the subject of medical research, but have not yet reached the clinical phase. For this reason, Epstein’s syndrome is currently considered incurable. At present, treatment is purely symptomatic. Platelet deficiency can be compensated, for example, by platelet concentrates or a platelet transfusion. This is particularly necessary in the context of surgery or injury to initiate the clotting cascade and keep the patient’s bleeding tendency under control. Hearing aids or later implants are usually offered to combat progressive hearing loss. Kidney symptoms are treated separately. For the kidney inflammation, patients can be given the anti-inflammatory agent methylprednisolone in high doses. This therapy is usually administered over several days and corresponds to a so-called shock therapy. Additional agents such as cyclophosphamide suppress the immune system. An alternative treatment method to the drug treatment of renal inflammation is blood filtration in the form of plasmapheresis. However, in the setting of Epstein’s syndrome, anti-inflammatory drug treatment is given priority because the disease is not an autoimmune disorder.

Outlook and prognosis

Epstein syndrome offers the affected individual no prospect of a cure. The prognosis is unfavorable because it is a gene disease. Interference with human genetics is prohibited to scientists and physicians under current legal guidelines.Therefore, the treating physicians can direct their focus exclusively on symptomatic treatment and try to minimize the existing complaints. Although the changes and complaints are already manifested when the affected person is born, a diagnosis is often only made later in the developmental process. The limitations or loss of hearing are treated by hearing aids as well as surgical interventions. Implants are used which lead to an improvement of the hearing power. These possibilities are to be understood as aids. Limitations and impairments of the hearing ability remain despite all efforts. The disturbances of the kidney activity are normally treated by the administration of medicines. If the course of the disease is favorable, the patient undergoes a shock therapy in which the renal function is stabilized and optimized. If the organism does not accept the active substances sufficiently, a filtering of the blood is applied. This significantly impairs the patient’s quality of life. Consequential diseases are possible at any time in Epstein’s syndrome. In addition to the physical sequelae, mental illnesses can develop. Both have a negative impact on the overall prognosis of the affected person.

Prevention

Epstein syndrome is based in particular on genetic factors. Therefore, to date, the disease can only be prevented by genetic counseling during family planning. If there is a familial predisposition to the disease, potential parents may decide against having children of their own.

Follow-up

With epispadias, the patient usually has very limited options for aftercare. The affected person is primarily dependent on medical examination and treatment by a physician to permanently alleviate the symptoms of epispadias. If the disease is not treated in time, it can lead to serious complications and discomfort that can significantly complicate the patient’s life. Therefore, in the first place, early diagnosis should be carried out. Epispadias are usually treated by surgical intervention. There are no particular complications, but the patient should rest and take care of his body after the operation. Complete recovery can only be achieved through strict bed rest. As a rule, strenuous and stressful activities should also be avoided. In many cases, even after successful treatment, those affected are dependent on regular examinations by a doctor, above all to guarantee proper wound healing. At the same time, care and support from one’s family or friends also has a positive effect on the course of epispadias and can prevent psychological upsets. The life expectancy of the affected person is usually not limited by this disease.

What you can do yourself

Epstein syndrome is a hereditary disease that manifests itself predominantly by platelet deficiency, impaired hearing, and chronic kidney inflammation. There are currently no conventional or alternative methods to treat Epstein’s syndrome causally, as the disease is genetic. For this reason, no preventive measures are possible. However, potential carriers of the hereditary disease should seek counseling before starting a family. During the counseling, the affected persons are informed about the probability of passing on the genetic defect to their offspring and about the consequences to be expected in case of an outbreak of the disease. If Epstein’s syndrome has already occurred in a family, those affected should always point this out to an attending physician. This also applies in the case of minor procedures, for example at the dentist. The lack of platelets characteristic of the disease can also be dangerous during basically harmless procedures, such as the extraction of a tooth. In some sufferers, the disease is accompanied by a deterioration in hearing. High-pitched sounds in particular can usually no longer be perceived. However, patients do not have to simply accept this symptom of the disease. They can usually be helped with a hearing aid or implants.