May-Hegglin anomaly is a rare, inherited disorder that primarily impacts blood platelets and white blood cells. It has an estimated prevalence of less than 1 in 1,000,000 individuals, affecting both males and females equally across various ethnic groups worldwide. This lifelong condition stems from a genetic mutation.
The Genetic and Cellular Basis
May-Hegglin anomaly is caused by a mutation in the MYH9 gene. This gene provides instructions for making non-muscle myosin IIA (NMMHC-IIA), a protein important for various cellular functions, including changes in cell shape and movement. The disorder is inherited in an autosomal dominant pattern, meaning only one copy of the mutated gene is sufficient for an individual to develop the condition.
The mutation in the MYH9 gene leads to the abnormal production of NMMHC-IIA. This abnormality disrupts the normal development and fragmentation of megakaryocytes, which are the large cells in the bone marrow responsible for producing platelets. The result is macrothrombocytopenia, characterized by abnormally large platelets, often two to five times larger than normal red blood cells, and a reduced platelet count.
Additionally, the altered NMMHC-IIA protein can precipitate within the cytoplasm of certain white blood cells, specifically neutrophils, eosinophils, and monocytes. These precipitates form distinctive, crescent-shaped inclusions known as Döhle bodies, which are typically large. While these cellular abnormalities are characteristic, the overall function of neutrophils and the platelets that do form is considered normal. The MYH9 gene is also linked to a group of related disorders that involve similar macrothrombocytopenia and leukocyte inclusions, sometimes with additional features.
Common Signs and Symptoms
The manifestations of May-Hegglin anomaly can vary significantly among affected individuals. Some people with the condition may not experience any symptoms at all, with the disorder being discovered incidentally during routine blood tests. However, about half of reported patients exhibit a low platelet count, often below 50,000 platelets per microliter, and abnormal bleeding.
When symptoms are present, they are primarily related to the reduced number and dysfunctional nature of platelets, which are blood components responsible for forming clots. Common bleeding-related issues include easy bruising, frequent nosebleeds, and bleeding gums. Women may experience heavy menstrual bleeding.
Individuals may also notice red, purple, or brown spots on their skin, a condition known as purpura. There is also an increased risk of prolonged or excessive bleeding after minor injuries, surgical procedures, or dental work. The severity of these bleeding symptoms depends on how low the platelet count is.
Diagnosing May-Hegglin Anomaly
Diagnosis of May-Hegglin anomaly begins with initial clues from routine blood tests. A complete blood count (CBC) may reveal a low platelet count, typically ranging from 40,000 to 80,000 platelets per microliter, along with the presence of abnormally large platelets. For reference, a platelet count below 150,000 per microliter is considered low.
Following initial blood test findings, a microscopic examination of a peripheral blood smear is performed. This detailed examination helps identify the characteristic abnormally large platelets and the distinctive Döhle bodies within white blood cells, particularly in neutrophils. These inclusions are a hallmark feature of the disorder.
A definitive diagnosis is confirmed through genetic testing, which aims to identify specific mutations in the MYH9 gene. This testing helps to confirm the diagnosis and can differentiate May-Hegglin anomaly from other bleeding disorders that might present with similar symptoms. Genetic testing can also aid in prognosis and genetic counseling for affected families.
Management and Outlook
There is currently no cure for May-Hegglin anomaly, and management focuses on preventing and treating bleeding episodes. Most individuals do not experience clinically significant bleeding problems and may not require specific treatment. However, awareness of potential bleeding risks is important, especially before surgical procedures or in cases of severe trauma.
Supportive care strategies include avoiding medications that can impair platelet function, such as aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), to minimize bleeding risk. In situations where there is a heightened risk of bleeding, such as before surgery or in cases of severe bleeding, platelet transfusions may be necessary to restore platelet levels. Desmopressin may also be used to prevent excessive bleeding during medical procedures.
Regular monitoring of blood counts is recommended to track platelet levels and assess bleeding risk. Genetic counseling is also important for affected families to help them understand the condition and its implications for future generations. While May-Hegglin anomaly is a lifelong condition, many individuals experience a relatively mild course and the disorder does not significantly interfere with their lives.