May-Hegglin Anomaly Clinical Presentation

  • Author: Vikramjit S Kanwar, MD, MBA, MRCP(UK), FAAP; Chief Editor: Robert J Arceci, MD, PhD   more...
 
Updated: Mar 29, 2012
 

History

Individuals with May-Hegglin anomaly (MHA) are often asymptomatic. The bleeding tendency associated with May-Hegglin anomaly is generally mild and is thought to mainly depend on the degree of thrombocytopenia.[8]

Symptoms of bleeding can include the following:

  • Recurrent epistaxis
  • Gingival bleeding
  • Easy bruising
  • Menorrhagia
  • Excessive bleeding associated with surgical procedures
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Physical

Physical findings are often normal. Findings of abnormal bleeding may be subtle. Bruising, which may or may not be associated with a history of clinically significant trauma, may be noted.

Petechiae may be present on the skin and are most common in pressure-point areas (eg, neck, overlying the clavicles, on the waist, areas where clothes are tight). Petechiae are associated with restricting conditions, such as the application of a tourniquet for venipuncture. Petechiae may also be observed on the oral and nasal mucosal surfaces.

Active bleeding from the mucosal surfaces may be observed. The most common sites of bleeding include the mouth and nose. Prolonged and excessive bleeding and oozing associated with lacerations and sutures may also be observed.

Looking for the associated clinical features of MYH9 -related disorders is important in enabling an accurate diagnosis. In patients initially thought to have May-Hegglin anomaly or Sebastian syndrome, the following findings were noted:[15]

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Causes

May-Hegglin anomaly is one of a family of macrothrombocytopenias characterized by mutations in the MYH9 gene, which is present at chromosomal region 22q12-13 and codes for nonmuscle myosin heavy-chain IIA.[2] The Döhlelike leukocyte inclusions in MHA are due to precipitation of myosin heavy chains in leukocytes.

Analysis of more than 70 families confirms that mutations in MYH9 can lead to May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, or Epstein syndrome.[16] In one fifth of individuals, the mutation may sporadically arise.[17] Macrothrombocytopenia is invariable, and the clinical features of these 4 entities are described below. The clinical description of these syndromes predated the discovery of the MYH9 gene mutations. Although the theory was that genotype-phenotype correlations would be found, overall this has not been the case.[18] The MYH9 R702 mutation is reportedly associated with the smaller neutrophil inclusions seen in Sebastian syndrome, Fechtner syndrome, and Epstein syndrome.[19]

Table. Clinical Features of MYH9 -Related Thrombocytopenias[15] (Open Table in a new window)

ConditionMacrothrombocytopeniaGranulocyte inclusionsNephritis and DeafnessCataracts
MHAYesLinear DöhlelikeNoNo
Epstein syndromeYesAbsent or faintYesNo
Fechtner syndromeYesSpherical granulesYesYes
Sebastian syndromeYesSpherical



granules



NoNo
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Proceed to Differential Diagnoses
 
 
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.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Frank E. Shafer, MD, to the development and writing of this article.

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. Antonio G, Silvia V, Emanuela B, Fabrizio F. Thrombotic events in MYH9 gene-related autosomal macrothrombocytopenias (old May-Hegglin, Sebastian, Fechtner and Epstein syndromes). J Thromb Thrombolysis. Nov 2011;32(4):474-7. [Medline].

  15. 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].

  16. 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].

  17. 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].

  18. 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].

  19. 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].

  20. 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].

  21. 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].

  22. 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].

  23. 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[15]
ConditionMacrothrombocytopeniaGranulocyte inclusionsNephritis and DeafnessCataracts
MHAYesLinear DöhlelikeNoNo
Epstein syndromeYesAbsent or faintYesNo
Fechtner syndromeYesSpherical granulesYesYes
Sebastian syndromeYesSpherical



granules



NoNo
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