May Hegglin Anomaly: Symptoms, Types, Causes and Treatment

May Hegglin Anomaly (MHA) is a rare genetic blood disorder that often goes unrecognized. Despite its rarity, understanding MHA is essential for patients, their families, and healthcare providers, as its symptoms can range from mild to potentially life-threatening. This article will walk you through the main aspects of MHA—its symptoms, types, causes, and treatments—based on the latest scientific research.

Symptoms of May Hegglin Anomaly

May Hegglin Anomaly presents a unique cluster of symptoms that can vary significantly from person to person. Some individuals may have subtle signs, while others can experience severe complications. The hallmark features—thrombocytopenia (low platelet count), giant platelets, and distinctive inclusion bodies in white blood cells—are often discovered incidentally during routine blood tests.

Symptom	Description	Severity Range	Sources
Thrombocytopenia	Low platelet count, often moderate to severe	Mild to Severe	1 3 5
Giant Platelets	Abnormally large platelets in blood	Variable	1 3 5
Leukocyte Inclusions	Döhle-like bodies in granulocytes	Present in most cases	1 3 5 7
Bleeding Diathesis	Easy bruising, nosebleeds, heavy periods	Absent to Severe	1 4 11
Purpura	Purple skin spots due to bleeding	Occasional	5
Hearing Loss	Sensorineural, high-frequency	Sometimes present	2 6 7
Cataracts	Clouding of the eye’s lens	Sometimes present	2 6 7
Kidney Issues	Proteinuria, nephritis	Sometimes present	2 6 7 10

Table 1: Key Symptoms

Symptom Details and Clinical Presentation

Thrombocytopenia and Bleeding

• Thrombocytopenia, or a persistently low platelet count, is the most consistent symptom of MHA. Platelet counts can range from mildly reduced to severely low (e.g., 14,000–178,000/mm³), but the severity of bleeding does not always correlate with the platelet count 1 12.
• Bleeding manifestations can include easy bruising, nosebleeds, heavy menstrual bleeding, and, rarely, serious internal bleeding. Interestingly, some individuals may have very low platelets but little to no bleeding, while others bleed more easily even with higher counts 1 4 12.

Giant Platelets and Leukocyte Inclusions

• Giant platelets are larger than normal platelets and can be seen under a microscope. Their presence can be a diagnostic clue for clinicians 1 3.
• Leukocyte inclusions, also called Döhle-like bodies, are bluish cytoplasmic inclusions seen in granulocytes. These are aggregates of the mutated protein and are a hallmark of the condition 1 3 5.

Systemic Features

• Some individuals, especially those with related MYH9 mutations, may develop:
  • Sensorineural hearing loss: typically high-frequency 2 6 7.
  • Cataracts: clouding of the lens, which can affect vision 2 6 7.
  • Kidney involvement: proteinuria, nephritis, and, in severe cases, kidney failure 2 6 7 10.

Variable Presentation

• MHA can be silent or cause significant health challenges. Many cases remain undiagnosed until adulthood or are discovered incidentally due to unexplained bleeding or during blood tests for unrelated reasons 1 3.

Types of May Hegglin Anomaly

While "May Hegglin Anomaly" is the classic diagnosis, research has revealed a spectrum of related disorders, collectively known as MYH9-related diseases. These syndromes share core features but differ in their additional symptoms.

Type/Syndrome	Key Features	Overlap/Distinctiveness	Sources
May-Hegglin Anomaly	Classic triad: thrombocytopenia, giant platelets, leukocyte inclusions	Baseline disorder	3 5 6
Sebastian Syndrome	Similar triad, different inclusion ultrastructure	Overlaps with MHA	6 7
Fechtner Syndrome	Triad + hearing loss, cataracts, nephritis	More systemic involvement	2 6 7
Epstein Syndrome	Triad + variable kidney and hearing issues	Overlaps with FTNS	2 6 7
MYH9-Related Disease	Broad clinical spectrum encompassing above syndromes	Unified entity	7

Table 2: Types of MHA and Related Disorders

Spectrum of MYH9-Related Disorders

May-Hegglin Anomaly (MHA)

• The classic form, defined by the triad of thrombocytopenia, giant platelets, and leukocyte inclusions.
• Traditionally thought to be "benign," but bleeding risk can range from mild to severe 1 3 5.

Sebastian Syndrome

• Very similar to MHA, with subtle differences in the structure of leukocyte inclusions.
• Clinical manifestations are nearly indistinguishable from classic MHA 6 7.

Fechtner and Epstein Syndromes

• Fechtner Syndrome: Adds non-hematological symptoms—especially sensorineural hearing loss, cataracts, and kidney disease—to the classic triad 2 6 7.
• Epstein Syndrome: Similar to Fechtner, but with variable expression of hearing and kidney abnormalities 2 6 7.

Unified Spectrum: MYH9-Related Disease

• Recent studies show there is significant overlap among these syndromes, all caused by mutations in the MYH9 gene 7.
• The clinical picture ranges from isolated blood abnormalities to multisystem involvement (hearing, vision, kidney).
• Therefore, experts now refer to this group as "MYH9-related disease," reflecting a single disorder with variable expression 7.

Causes of May Hegglin Anomaly

Understanding the root cause of MHA provides insight into both its symptoms and its inheritance pattern. The disorder is fundamentally a genetic disease affecting platelet production and structure.

Cause	Key Details	Inheritance	Sources
MYH9 Gene Mutations	Defects in nonmuscle myosin heavy chain IIA (NMMHC-IIA)	Autosomal dominant	2 3 5 6 8
Chromosome Location	22q12–13 region	Familial	8 9
Protein Dysfunction	Abnormal cytoskeleton in megakaryocytes	Inherited	2 8
Pathogenic Mechanism	Impaired platelet formation, inclusion body aggregation	Hereditary	2 3 8

Table 3: Underlying Causes of May-Hegglin Anomaly

Genetic and Molecular Basis

MYH9 Gene Mutations

• MHA is caused by mutations in the MYH9 gene, which encodes the protein nonmuscle myosin heavy chain IIA (NMMHC-IIA) 2 3 5 6 8.
• This protein is essential for the structure and function of the cytoskeleton in many cell types, especially megakaryocytes (the bone marrow cells that produce platelets) 2 8.

Inheritance Pattern

• The disorder is inherited in an autosomal dominant fashion. This means a single copy of the mutated gene, from either parent, is enough to cause the disease 3 5 6.
• Family history is common, but new (de novo) mutations can also occur 8.

Pathogenesis: How the Mutation Causes Disease

• Mutations in MYH9 disrupt the normal organization of the cytoskeleton in megakaryocytes, leading to abnormal platelet production and the formation of giant, sometimes dysfunctional platelets 2 8.
• The same protein aggregates in white blood cell cytoplasm, forming the characteristic inclusion bodies 3.
• In some cases, unstable or truncated protein leads to more severe, systemic involvement, such as hearing, eye, and kidney problems 2 6 7.

No Clear Genotype-Phenotype Correlation

• Although different mutations are identified in MYH9, predicting the severity or specific symptoms based on genetic testing alone is difficult 2 7.
• The same mutation may cause a mild form in one person and a more severe form in another, even within the same family 7.

Treatment of May Hegglin Anomaly

Managing MHA focuses on preventing and treating bleeding episodes, supporting patients during high-risk situations (such as surgery or childbirth), and monitoring for systemic complications. While there is no cure, several strategies can improve quality of life.

Treatment Approach	Description	Use Case/Effectiveness	Sources
Supportive Care	Avoidance of trauma; careful monitoring	Most patients	1 11 12
Platelet Transfusions	Used for severe bleeding or surgery	Acute situations	14 15
Desmopressin (DDAVP)	Shortens bleeding time	Surgical/procedure prep	1 11 14 15
Immunosuppressives	Corticosteroids, IVIG—generally ineffective	Not recommended	1
Splenectomy	No proven benefit	Not recommended	1
Anesthesia Management	Neuraxial techniques possible	Pregnancy/delivery	12 13
Monitoring Complications	Hearing, kidney, and eye screening	Long-term management	7 10

Table 4: Treatment Options for May-Hegglin Anomaly

Management Strategies

General Supportive Care

• Most patients do not require daily treatment; education about avoiding unnecessary trauma or medications that increase bleeding risk (e.g., NSAIDs) is key 1 11.
• Patients should be informed of their bleeding risk, and medical alert identification is recommended.

Managing Bleeding Episodes

• Platelet transfusions may be used for active bleeding or before invasive procedures 14 15.
• Desmopressin (DDAVP), a medication that can enhance platelet function and shorten bleeding time, has been effective in some patients, especially prior to surgery 1 11 14 15.

Ineffective or Not Recommended Treatments

• Corticosteroids, intravenous immunoglobulins (IVIG), and splenectomy have not demonstrated benefit and are not recommended for treatment of thrombocytopenia in MHA 1.

Surgical and Obstetric Care

• MHA patients can safely undergo major surgery (even with low platelets) when managed with desmopressin and/or platelet transfusion as needed 11 12 14 15.
• Neuraxial anesthesia (such as epidurals) has been successfully used during childbirth in women with MHA without complications 12 13.

Monitoring and Managing Systemic Complications

• Regular screening for hearing loss, cataracts, and kidney disease is crucial, especially for patients with MYH9 mutations that are associated with these features 7 10.
• Early intervention for these complications can improve long-term outcomes.

Conclusion

May Hegglin Anomaly is a rare but important inherited blood disorder. While it can present with only mild symptoms in some, others may face significant bleeding risks or systemic complications. Advances in genetic understanding have unified what were once thought to be separate syndromes under the umbrella of MYH9-related diseases.

Key Takeaways:

• MHA is characterized by thrombocytopenia, giant platelets, and leukocyte inclusions; bleeding risk varies widely.
• Hearing loss, cataracts, and kidney disease are possible in more severe or systemic forms.
• All MYH9-related disorders represent a clinical spectrum, not distinct diseases.
• The cause is mutation in the MYH9 gene, with autosomal dominant inheritance.
• There is no cure, but supportive care, desmopressin, and platelet transfusions can be effective.
• Most patients live normal lives with appropriate management and monitoring.

By recognizing the signs and understanding the underlying causes and management strategies, patients and clinicians can work together to minimize risks and ensure the best possible outcomes.