May-Hegglin anomaly is an inherited abnormality of leukocytes that is one of the MYH9-associated disorders and is associated with a point mutation. The inherited disorder is associated with a deficiency of platelets and an abnormal platelet shape. Patients with the abnormality therefore suffer from mild bleeding tendencies.
What is a May-Hegglin anomaly?
The group of so-called MYH9-associated diseases includes various inherited disorders that have a mutation in the MYH6 genes as their basis. This group of diseases includes May-Heggelin anomaly, which is associated with altered platelets and is included among the genetic leukocyte abnormalities. Other disorders in the MYH9-associated group include Sebastian syndrome, Fechtner syndrome, and Epstein syndrome. May-Hegglin anomaly is the most common disease from the parent group, although it is also a rare disease. To date, not enough cases have been documented to give a reliable prevalence. The small number of cases makes research on May-Hegglin anomaly and the other MYH9-associated disorders difficult. For this reason, not all associations of the disease group have been conclusively established.
Causes
The cause of MHA is a genetic mutation. It is a point mutation in the MYH9 gene located on chromosome 22 and gene locus q11.2. This gene encodes heavy chains of type IIA non-muscle myosin. This is a protein found primarily in blood cells such as monocytes and platelets, and within the cochlea and kidneys. Mutation of the gene results in a conformational change affecting the head of the NMMHC-IIA protein. The protein of the patients aggregates abnormally into Döhle bodies because of the conformational change, and the cytoskeleton of the megakaryocytes organizes incorrectly as a consequence. Megakaryocytes are precursor cells of platelets. Thus, mutation of the gene in the context of May-Hegglin anomaly leads not only to leukocyte abnormality, but also to macrothrombocytopenia. This phenomenon is characterized by a deficiency of platelets resulting from oversized platelets. The hyperplastic platelets carry leukocyte inclusions and sometimes become even larger than erythrocytes. Familial clustering has been observed for the anomaly. The disease is passed on in an autosomal dominant inheritance.
Symptoms, complaints, and signs
Patients with May-Hegglin anomaly suffer from a number of characteristic clinical symptoms. The symptom complex includes a decreased platelet count and altered platelet volume. Because of these associations, they are usually affected by increased bleeding tendency, as platelets play a major role in the coagulation cascade. The symptomatic bleeding tendency of these patients is not as pronounced as in patients of the related Sebastian syndrome. Nevertheless, patients of May-Hegglin anomaly also suffer from platelet dysfunction, also known as thrombocytopathy. These symptoms are associated with macrothrombocytopenia, which is indicated by the presence of platelets inform an abnormal size with leukocyte inclusions. Affected individuals, unlike patients with Fechtner syndrome or Epstein syndrome, do not have hearing loss or renal problems. The abnormality is usually referred to as the mildest disease from the range of MYH9-associated disorders because it is associated with the fewest symptoms and the mildest expression.
Diagnosis and disease course
Diagnosis of May-Hegglin anomaly may be challenging for physicians. Some patients show few symptoms and therefore are not diagnosed at all or are diagnosed at an older age. Because of the approximate lack of symptoms, the history often does not take the physician very far. Often, only routine blood tests reveal abnormalities. On closer examination, these may suggest a disease from the group of MYH9-associated disorders. In order to differentiate the diseases from this group, a molecular genetic analysis must be performed. Although all four diseases from this group manifest as point mutations of the MYH9 gene, these point mutations are localized at different sites depending on the disease.For this reason, DNA analysis allows a definitive diagnosis to be made on the anomaly. The prognosis is extremely favorable. There are usually no restrictions on life expectancy or daily life for those affected.
Complications
May-Hegglin anomaly causes increased bleeding in patients. These occur even with minor injuries or cuts and are very difficult to stop in most cases. The quality of life of the affected person is significantly limited and reduced by May-Hegglin anomaly. In some cases, May-Hegglin anomaly can also lead to hearing loss and thus to further limitations in the patient’s daily life. Similarly, kidney problems occur, so that in the worst case the affected person may suffer from kidney failure. Sufferers are dependent on regular examinations and controls to avoid various consequential damages. Unfortunately, a direct and causal treatment of May-Hegglin anomaly is not possible. Therefore, treatment is primarily aimed only at limiting the symptoms. However, in many cases of May-Hegglin anomaly, no treatment is necessary if there is no damage or restriction to the internal organs. Affected individuals must be aware of and avoid various hazards in their daily lives to prevent bleeding. In acute emergencies, bleeding can be stopped with the help of medication. In most cases, life expectancy is not reduced by May-Hegglin anomaly.
When should you see a doctor?
People who show an increased tendency to bleed compared directly with their peers should see a doctor. If even small wounds can only be stopped with great effort or after a high blood loss, a visit to the doctor is advisable. In addition, sterile wound care is needed to prevent the risk of sepsis and thus danger to life. If wound care cannot be provided by the affected person to the extent required, a doctor should be consulted as soon as possible. If existing wounds tear again very quickly during a dressing change, this is an indication of an existing irregularity. An optimal healing process is considerably disturbed by this and should be examined by a doctor. If the affected person suffers from frequent nose or gum bleeding, it is advisable to discuss the observations with a physician. If dizziness, blurred vision or loss of internal strength occurs due to increased blood loss, a physician is needed. Extensive examinations are necessary to determine a cause and allow a diagnosis to be made. If there is a loss of consciousness, emergency medical services should be alerted. There is a potentially life-threatening condition that must be attended to by a physician. If sexually mature women suffer from heavy menstrual bleeding, they should log the amount of blood and then consult a physician. If there is a loss of hearing, a physician is also needed.
Treatment and therapy
Causal therapy is not available for any of the MYH9-associated disorders. May-Hegglin anomaly is also considered incurable to date because of its genetic basis. Currently, gene therapy approaches are a subject of medical research. For this reason, a causal treatment for the anomaly may exist in the near future that will make the disease a curable condition. So far, this is still a thing of the future. Symptomatic treatments can be given to May-Hegglin anomaly patients as needed. In most cases, however, therapies are not necessary. Most of those affected have almost no limitations at all as a result of the disease. Even in the case of minor injuries, the disease does not usually lead to serious complications or unacceptably high blood loss, as the patients’ bleeding tendency is kept within limits. In the context of serious injuries and operations, patients are usually nevertheless given a platelet concentrate to compensate for the platelet deficiency and to promote coagulation. Bleeding complications can be prevented in this way.
Outlook and prognosis
The prognosis in terms of life expectancy is positive in almost all patients with May-Hegglin anomaly. The mutation-related inherited disease has become known as the most common among the very rare MYH9-associated diseases. By means of symptomatic therapy, May-Hegglin anomaly can be kept stable.Only before upcoming operations a platelet transfusion is necessary. Only surgical and postoperative risks can worsen the prognosis. The fact that the prognosis for May-Hegglin anomaly is so favorable is a stroke of luck. However, those affected suffer from an increased bleeding tendency due to this condition. However, this is not comparable to hemophilia. It is much weaker. There are usually no other symptoms. Therefore, this form of MYH9-associated disease can be easily distinguished from the other forms of this group. However, it is problematic that some patients with this anomaly have no symptoms at all. Some therefore only become conspicuous at an advanced age. Without a molecular genetic examination or a DNA analysis, the physician will not have any clarity as to which of the four diseases of this form group is present. So far, only a few cases of May-Hegglin anomaly have been reported. Therefore, no statements can be made about the prevalence of the anomaly so far. Doctors only know that May-Hegglin anomaly is inherited in an autosomal dominant manner. It therefore runs in families. Since the prognosis is favorable, no life-limiting consequences of the disease are to be expected.
Prevention
The diseases in the MYH9-associated group are all extremely rare disorders. For this reason, research within the disease group has not progressed far enough for preventive measures to be available. Because of the heritability of May-Hegglin anomaly, patients with this disorder may at least seek genetic counseling during family planning.
Follow-up
May-Hegglin anomaly is usually associated with various medical conditions, all of which can have a very negative impact on the life and also the quality of life of the affected person. Therefore, the affected person should contact a physician at the first symptoms or signs of the disease to prevent the symptoms from continuing to worsen. Due to the increased bleeding tendency, sufferers should take care to lead a mindful lifestyle to mitigate the risk of injury. Insofar as the symptoms of the disease have promoted the development of psychological problems or even depression, a psychologist should be consulted. Adjunctive therapy can help restore mental balance and promote better coping with the disease.
Here’s what you can do yourself
Because affected individuals suffer from a markedly increased tendency to bleed due to May-Hegglin anomaly, any bleeding must be avoided. This includes avoiding dangerous sports or accidents. Also, during surgical procedures or various other medical examinations, the attending physician should always be informed about May-Hegglin anomaly. If both parents have this anomaly, genetic counseling may be useful if the child is desired. Thereby the risk of inheritance of this disease can be estimated. If bleeding occurs in the patient, it must be stopped. In most cases it is not necessary to see a doctor, but stopping the bleeding can take a little longer. Major blood loss does not occur and there are no further complications. In case of surgical interventions, patients are dependent on taking medication to prevent severe bleeding. No further treatment of the May-Hegglin anomaly is necessary. In most cases, the development of the child is also not negatively affected by the condition, so no treatment is necessary in this case either.
