Information on the following diseases can be found in the Related Disorders section of this report:

• Hemophilia
• Bernard-Soulier Syndrome
• Storage Pool Disease
• Essential Thrombocytopenia
• Thrombasthenia of Glanzmann and Naegeli
• von Willebrand Disease
• Platelet Disorders (General)

Some people with May-Hegglin Anomaly may have symptoms at birth while others may have no symptoms throughout their lifetime. Symptoms may include red or purple colored spots on the skin (purpura), nose bleeds (epitaxis), excessive bleeding from the mouth during dental work, headaches, and/or muscle weakness on one side of the body due to bleeding within the brain (intracranial bleeding).

Excessive bleeding may occur in some people with May-Hegglin Anomaly when steroid drugs used to treat another disorder are discontinued.

May-Hegglin Anomaly is inherited as an autosomal dominant genetic trait. The gene involved has been mapped to Gene Map Locus 22q11.2, and the protein generated by the gene is known as MYH9.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
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May-Hegglin Anomaly is a rare blood platelet disorder that affects males and females in equal numbers. It occurs more often in people of Greek or Italian descent than among others. As of about 10 years ago, only about 170 cases were reported in the literature.
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Symptoms of the following disorders can be similar to those of May-Hegglin Anomaly. Comparisons may be useful for a differential diagnosis:

Hemophilia is a rare inherited blood clotting (coagulation) disorder caused by inactive or deficient blood proteins (usually factor VIII). Factor VIII is one of several proteins that enables the blood to clot. Hemophilia is found in males almost exclusively and can be classified as mild, moderate, or severe. The most serious symptom of Hemophilia is uncontrolled internal bleeding that may begin spontaneously without any apparent cause. Internal bleeding may cause permanent damage to the joints and muscles. People with Hemophilia bleed for a longer period of time than people who have the normal percentage of active clotting factors in their blood. Bruises and trauma can trigger episodes of serious internal bleeding in males with this disorder. (For more information on this disorder, choose "Hemophilia" as your search term in the Rare Disease Database.)

Bernard-Soulier Syndrome is a rare inherited blood clotting (coagulation) disorder characterized by abnormalities of platelets. Symptoms include a tendency to bleed excessively and bruise easily. People with Bernard-Soulier Syndrome tend to bleed profusely from cuts and other injuries. Nosebleeds and unusually heavy menstrual flow in women are also common. Bleeding under the skin may cause small or large purple colored spots (purpura) in different areas of the body. (For more information on this disorder, choose "Bernard- Soulier" as your search term in the Rare Disease Database.)

Storage Pool Disease (SPD) is a rare inherited disorder of blood platelets characterized by clotting dysfunction due to the platelets' inability to store certain clotting factors. Symptoms occur mostly in women and may include mild bleeding, nosebleeds, and slightly heavier than normal menstrual periods. People with Storage Pool Disease may also have abnormally low levels of blood platelets (thrombocytopenia).

Essential Thrombocytopenia is a rare blood platelet disorder characterized by an abnormally small number of circulating platelets that survive for a shorter than normal period of time. The major symptom is excessive hemorrhaging, especially under the skin, in the eyes, and in the mucous membranes of the mouth. In severe cases of Essential Thrombocytopenia abnormal bleeding may occur in the brain (intracranial hemorrhage). People with this disorder bruise easily and may also have sudden nosebleeds. Many small red or purple spots (petechiae) may appear on the skin, especially around the ankles and feet. (For more information on this disorder, choose "Essential Thrombocytopenia" as your search term in the Rare Disease Database.)

Thrombasthenia of Glanzmann and Naegeli is a rare inherited blood clotting (coagulation) disorder characterized by the impaired function of the specialized red blood cells (platelets) that are essential for proper blood clotting. Symptoms may include abnormal bleeding and/or hemorrhage, easy bruising, bleeding from the gums, nosebleeds (epitaxis), and/or large red or purple colored spots on the skin (purpura). The symptoms of Thrombasthenia of Glanzmann and Naegeli are not progressive and may improve with age. (For more information on this disorder, choose "Thrombasthenia" as your search term in the Rare Disease Database.)

Von Willebrand Disease is a rare inherited blood clotting (coagulation) disorder that occurs during infancy or early childhood and is characterized by prolonged bleeding and an abnormally slow blood clotting time. Symptoms may include bleeding from the gastrointestinal tract, nosebleeds, bleeding from the gums, and/or easy bruising. People with this disorder may also bleed easily after injury, childbirth, and/or surgery. These symptoms occur because of a deficiency of factor VIII and the von Willebrand factor. (For more information on this disorder, choose "von Willebrand" as your search term in the Rare Disease Database.)

Platelet disorders are also associated with congenital conditions such as Wiskott-Aldrich Syndrome, Down Syndrome, Thrombocytopenia with Absent Radius Syndrome, and Chediak-Higashi Syndrome. (For more information on these disorders choose "Wiskott-Aldrich," "Down Syndrome" "Thrombocytopenia with Absent Radius," and "Chediak-Higashi" as your search terms in the Rare Disease Database.)

The diagnosis of May-Hegglin Anomaly is made by specialized blood tests that reveal giant, oddly shaped platelets and characteristic cellular "inclusions" in certain white blood cells (leukocytes). There also might be fewer platelets than normal (mild thrombocytopenia). In severe rare cases, people with May-Hegglin Anomaly may require transfusions of platelets. People with Chediak-Higashi Syndrome, a form of Albinism, have cellular inclusions that are very similar to those of May-Hegglin Anomaly.

Pregnant women with May-Hegglin Anomaly may experience episodes of bleeding. Therefore, expectant mothers and their unborn children should be monitored for abnormal bleeding and/or hemorrhages.

May-Hegglin Anomaly generally does not require therapy in mild cases. Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Research on genetic disorders and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic and familial disorders in the future.

McKusick VA, Ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Entry Number; 155100: Last Edit Date; 4/6/2001.

McKusick VA, Ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Entry Number; 153640: Last Edit Date; 1/17/2001.

McKusick VA, Ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Entry Number; 153650: Last Edit Date; 5/10/2002.

McKusick VA, Ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Entry Number; 605249: Last Edit Date; 8/31/2000.

McKusick VA, Ed. ONLINE MENDELIAN INHERITANCE IN MAN (OMIM). The Johns Hopkins University. Entry Number; 160775: Last Edit Date; 1/16/2003.

TEXTBOOKS
NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:403-04.

Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:927.

Hoffman R, Benz Jr EJ, Shattil SJ et al. Eds. Hematology: Basic Principles and Practice. 2nd ed. Churchill-Livingstone, Inc. New York, NY; 1995:1875.

JOURNAL ARTICLES
Balduini CL, Iolascon A, Savoia A. Inherited thrombocytopenias: from genes to therapy. Haematologica. 2002;87:860-80.

Seri M, Savino M, Bordo D, et al. Epstein syndrome: another renal disorder with mutations in the nonmuscle myosin heavy chain 9 gene. Human Genet. 2002;110:182-86.

Fayyad AM, Brummitt DR, Barker HF, et al. May-hegglin anomaly: the role of aspirin in the treatment of this rare platelet disorder in pregnancy. BJOG. 2002;109:223-24.

Kunishima S, Matsushita T, Kojima T, et al. Identification of six novel MYH9 mutations and genotype-phenotype relationships in autosomal dominant macrothrombocytopenia with leukocyte inclusions. J Hum Genet. 2001;46:722-29.

Chabane H, Galiais Y, Pathier D, et al. Delivery management in a woman with thrombocytopenia of the may-Hegglin anomaly type. Eur J Obstet Gynecol Reprod Biol. 2001;99:124-25.

Heath KE, Campos-Barros A, Toren A, et al. Nonmuscle myosin heavy chain IIA mutations define a spectrum of autosomal dominant macrothrombocytopenias: May-Hegglin anomaly and Fechtner. Sebastian, Epstein, and Alport-like syndromes. Am J Hum Genet. 2001;69:1033-45.

Kelley MJ, Jawien W, Ortel TL, et al. Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly. Nat Genet. 2000;26:106-08.

Seri M, Cusano R, Gangarossa S, et al. Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The may-Hegglin/Fechtner Syndrome Consortium. Nat Genet. 2000;26:103-05.

Martignetti JA, Heath KE, Harris J, et al. The gene for may-Hegglin anomaly localizes to a ,1-Mb region of chromosome 22q12.3-13.1. Am J Hum Genet. 2000;66:1449-54.

FROM THE INTERNET
Puget Sound Blood Center. Types of Inherited Thrombocytopenia. nd. 3pp.
www.familygenetics.net/disorders/thrombocytopenia-types.htm

Martignetti JA. Five (un)easy pieces: the MYH9-related giant platelet syndromes. 9/2002. 3pp.
www.haematologica.ws/2000_09/897.htm

Shafer FE. May-Hegglin Anomaly. eMedicine. Last Updated: September 14, 2001. 8pp.
www.emedicine.com/ped/topic1383.htm