May-Hegglin Anomaly 

  • Author: Vikramjit S Kanwar, MD, MBA, MRCP(UK), FAAP; Chief Editor: Robert J Arceci, MD, PhD   more...
 
Updated: May 25, 2010
 

Background

In 1909, May described the presence of leukocyte inclusions and large platelets in an asymptomatic young woman. In 1945, Hegglin described a man and his 2 sons who were healthy but had a triad consisting of thrombocytopenia, giant platelets, and leukocyte inclusions (see the image below). This diagnostic triad was later given the eponym May-Hegglin anomaly (MHA).[1]

Blood smear (original magnification X2000) in a paBlood smear (original magnification X2000) in a patient with May-Hegglin anomaly (MHA) demonstrates a characteristic giant platelet with poorly defined granulation. A normal-sized platelet is also present. The trilobed neutrophil contains a large, well-defined, basophilic, peripherally placed cytoplasmic inclusion body (resembling a Döhle body). Used with permission from Little, Brown.

May-Hegglin anomaly is an autosomal dominant disorder characterized by various degrees of thrombocytopenia that may be associated with purpura and bleeding, giant platelets containing few granules, and large (2-5 µm), well-defined, basophilic, cytoplasmic inclusion bodies in granulocytes that resemble Döhle bodies.

May-Hegglin anomaly is one of a family of macrothrombocytopenias characterized by mutations in the MYH9 gene.[2] The other members of this family include Sebastian syndrome,[3] Epstein syndrome,[4] and Fechtner syndrome.[5]

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Pathophysiology

Patients have a mutation of the MYH9 gene present in chromosomal region 22q12-13.[6, 2] The mutation results in disordered production of nonmuscle myosin heavy-chain type IIA, which leads to invariable macrothrombocytopenia secondary to defective megakaryocyte maturation.[7] Platelet function in patients with May-Hegglin anomaly has been reported as normal.[8, 9] However, in one study, epinephrine response was described as abnormal in 8 of 15 patients.[10]

Leukocyte Döhlelike inclusion bodies are visualized on standard Wright stain and appear bright blue and spindle shaped. Ultrastructural studies reveal that these bodies consist of clusters of ribosomes oriented along parallel myosin heavy-chain filaments 7–10 nm in diameter.[11] Neutrophil function is considered to be normal, and patients have no increased susceptibility to infections.

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Epidemiology

Frequency

United States

May-Hegglin anomaly is a rare autosomal dominant disorder. In one review, 180 cases had been reported in the literature.[10] The exact incidence of the syndrome is unknown.

International

May-Hegglin anomaly is a rare autosomal dominant disorder, and the exact incidence is unknown. Kindreds have been reported from Italy, France, Germany, and North America.[2] May-Hegglin anomaly was reported in 15 families in Japan in 1993.[12]

Mortality/Morbidity

The rarity of May-Hegglin anomaly has led to conflicting literature regarding the risk for bleeding. Asymptomatic patients have been described.[8, 9] However, abnormal bleeding has also been documented.[10] The risk for excess bleeding with surgical procedures is unclear.[13]

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Contributor Information and Disclosures
Author

Vikramjit S Kanwar, MD, MBA, MRCP(UK), FAAP  Associate Professor of Pediatric Hematology and Oncology, Department of Pediatrics, Albany Medical Center; Faculty, Alden March Bioethics Institute

Vikramjit S Kanwar, MD, MBA, MRCP(UK), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and Royal College of Physicians of the United Kingdom

Disclosure: Nothing to disclose.

Specialty Editor Board

Gary R Jones, MD  Associate Medical Director, Clinical Development, Berlex Laboratories

Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Gary D Crouch, MD  Associate Professor, Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Uniformed Services University of the Health Sciences

Gary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology

Disclosure: Nothing to disclose.

Samuel Gross, MD  Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University

Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD  King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine

Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

References

  1. Saito H, Kunishima S. Historical hematology: May-Hegglin anomaly. Am J Hematol. Apr 2008;83(4):304-6. [Medline].

  2. Seri M, Cusano R, Gangarossa S, et al. Mutations in MYH9 result in the May-Hegglin anomaly, and Fechtner and Sebastian syndromes. The May-Heggllin/Fechtner Syndrome Consortium. Nat Genet. Sep 2000;26(1):103-5. [Medline].

  3. Greinacher A, Nieuwenhuis HK, White JG. Sebastian platelet syndrome: a new variant of hereditary macrothrombocytopenia with leukocyte inclusions. Blut. Nov 1990;61(5):282-8. [Medline].

  4. Epstein CJ, Sahud MA, Piel CF, Goodman JR, Bernfield MR, Kushner JH. Hereditary macrothrombocytopathia, nephritis and deafness. Am J Med. Mar 1972;52(3):299-310. [Medline].

  5. Peterson LC, Rao KV, Crosson JT, White JG. Fechtner syndrome--a variant of Alport's syndrome with leukocyte inclusions and macrothrombocytopenia. Blood. Feb 1985;65(2):397-406. [Medline].

  6. Kunishima S, Kojima T, Tanaka T, et al. Mapping of a gene for May-Hegglin anomaly to chromosome 22q. Hum Genet. Nov 1999;105(5):379-83. [Medline].

  7. Chen Z, Shivdasani RA. Regulation of platelet biogenesis: insights from the May-Hegglin anomaly and other MYH9-related disorders. J Thromb Haemost. Jul 2009;7 Suppl 1:272-6. [Medline].

  8. Burns ER. Platelet studies in the pathogenesis of thrombocytopenia in May-Hegglin anomaly. Am J Pediatr Hematol Oncol. Winter 1991;13(4):431-6. [Medline].

  9. Mayer K, Schildknecht O, von Felten A. [May-Hegglin anomaly: further studies on thrombocyte dysfunction]. Schweiz Med Wochenschr. Jun 28 1997;127(26):1134-40. [Medline].

  10. Noris P, Spedini P, Belletti S, et al. Thrombocytopenia, giant platelets, and leukocyte inclusion bodies (May- Hegglin anomaly): clinical and laboratory findings. Am J Med. Apr 1998;104(4):355-60. [Medline].

  11. Pujol-Moix N, Kelley MJ, Hernandez A, Muniz-Diaz E, Espanol I. Ultrastructural analysis of granulocyte inclusions in genetically confirmed MYH9-related disorders. Haematologica. Mar 2004;89(3):330-7. [Medline].

  12. Ishii A, Honnma T, Ishida M, Sano F, Hamada H, Takayanagi M. Pregnancy complicated by the May-Hegglin anomaly. J Perinat Med. 1993;21(3):247-52. [Medline].

  13. Sehbai AS, Abraham J, Brown VK. Perioperative management of a patient with May-Hegglin anomaly requiring craniotomy. Am J Hematol. Aug 2005;79(4):303-8. [Medline].

  14. Seri M, Pecci A, Di Bari F, et al. MYH9-related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. Medicine (Baltimore). May 2003;82(3):203-15. [Medline].

  15. Heath KE, Campos-Barros A, Toren A, Rozenfeld-Granot G, Carlsson LE, Savige J. 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. Nov 2001;69(5):1033-45. [Medline].

  16. Otsubo K, Kanegane H, Nomura K, Ogawa J, Miyawaki T, Kunishima S. Identification of a novel MYH9 mutation in a patient with May-Hegglin anomaly. Pediatr Blood Cancer. Dec 2006;47(7):968-9. [Medline].

  17. Dong F, Li S, Pujol-Moix N, et al. Genotype-phenotype correlation in MYH9-related thrombocytopenia. Br J Haematol. Aug 2005;130(4):620-7. [Medline].

  18. Kunishima S, Yoshinari M, Nishio H, Ida K, Miura T, Matsushita T. Haematological characteristics of MYH9 disorders due to MYH9 R702 mutations. Eur J Haematol. Mar 2007;78(3):220-6. [Medline].

  19. Kunishima S, Matsushita T, Kojima T, Sako M, Kimura F, Jo EK. Immunofluorescence analysis of neutrophil nonmuscle myosin heavy chain-A in MYH9 disorders: association of subcellular localization with MYH9 mutations. Lab Invest. Jan 2003;83(1):115-22. [Medline].

  20. Bizzaro N. May-Hegglin anomaly and uncomplicated vaginal delivery: a report of 41 cases. Am J Obstet Gynecol. Jul 1999;181(1):226-7. [Medline].

  21. Chabane H, Gallais Y, Pathier D, Tchernia G, Gaussem P. Delivery management in a woman with thrombocytopenia of the May-Hegglin anomaly type. Eur J Obstet Gynecol Reprod Biol. Nov 2001;99(1):124-5. [Medline].

  22. DiMichele DM, Hathaway WE. Use of DDAVP in inherited and acquired platelet dysfunction. Am J Hematol. Jan 1990;33(1):39-45. [Medline].

 
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Blood smear (original magnification X2000) in a patient with May-Hegglin anomaly (MHA) demonstrates a characteristic giant platelet with poorly defined granulation. A normal-sized platelet is also present. The trilobed neutrophil contains a large, well-defined, basophilic, peripherally placed cytoplasmic inclusion body (resembling a Döhle body). Used with permission from Little, Brown.
Table. Clinical Features of MYH9 -Related Thrombocytopenias[14]
ConditionMacrothrombocytopeniaGranulocyte inclusionsNephritis and DeafnessCataracts
MHAYesLinear DöhlelikeNoNo
Epstein syndromeYesAbsent or faintYesNo
Fechtner syndromeYesSpherical granulesYesYes
Sebastian syndromeYesSpherical



granules



NoNo
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