May-Hegglin anomaly is part of a spectrum of disorders called MYH9-related disease. Mutations in the MYH9 gene cause macrothrombocytopenia (low platelet count with large platelets) and basophilic inclusions in white blood cells. A diagnosis can be facilitated by platelet electron microscopy and MYH9 gene sequencing. While each disorder in the spectrum has some unique characteristics, they are all characterized by macrothrombocytopenia and are now considered manifestations of MYH9-related disease.

1. May-Hegglin anomaly
MYH9-related disease

6. May-Hegglin anomaly

7. May-Hegglin anomaly
• MYH9 mutations cause the inherited macro-
thrombocytopenic syndromes of May-Hegglin
anomaly, Fechtner syndrome, Sebastian
syndrome, and Epstein syndrome, collectively
referred to as MYH9-related disease.

8. • Diagnosis is facilitated by platelet electron
microscopy and MYH9 sequencing.

9. MYH9-related disorders
• — Mutations of the nonmuscle myosin heavy
chain gene, MYH9, result in hereditary
macrothrombocytopenia (although absence of
a relevant family history does not rule out the
disorder because 35 percent of mutations may
be sporadic). These were previously described
as four distinct disorders, based on clinical
features [28,29].

10. MYH9-related disorders
• The May-Hegglin anomaly is characterized by
giant platelets, mild to moderate
thrombocytopenia, and basophilic inclusions
in the peripheral blood leukocytes. Leukocyte
inclusions are similar in appearance to Döhle
bodies seen in infection.

11. MYH9-related disorders
• Fechtner, Epstein, and Sebastian syndromes are
also characterized by macrothrombocytopenia,
but vary between each other in terms of the
specific appearance of leukocyte inclusions, and
the presence or absence of sensorineural
deafness, cataracts, and nephritis. These four
diagnostic entities are now considered together
as the spectrum of MYH9-related disorders [30].
The risk for extra-hematological manifestations
(nephropathy and deafness) is correlated with
the specific MYH9 mutation [31].

12. Reference
• https://www.ncbi.nlm.nih.gov/pubmed/23007341