MYH9 related platelet disorders - often unknown and misdiagnosed

Klin Padiatr. 2011 May;223(3):120-5. doi: 10.1055/s-0031-1275664. Epub 2011 May 12.

Abstract

MYH9 related platelet disorders are a relatively rare cause of thrombocytopenia. Located on chromosome 22, the MYH9 gene encodes the motorprotein non-muscular myosin heavy chain IIA (NMMHCIIA). Heterozygous defects in this gene lead to 4 different autosomal dominant syndromes namely May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome and Sebastian platelet syndrome. All 4 syndromes are characterized by macrothrombocytopenia and a mild bleeding tendency. Depending on the position of the causative mutation within the gene, the risk increases for syndromic manifestations such as renal failure, hearing loss and pre-senile cataract. Mutations in the neck region of the NMMHCIIA protein are more likely associated with these comorbidities than mutations in the N- or C-terminal part of the gene. MYH9 related platelet disorders should be excluded in patients with chronic thrombocytopenia and large platelets. Most sensitive for diagnosis/exclusion are immunofluorescence studies using a blood smear. The biggest risk for these patients is ineffective but potentially harmful treatment based on the misdiagnosis of immune thrombocytopenia. This review provides a workflow for diagnosis and treatment of MYH9 related thrombocytopenia.

Publication types

  • Review

MeSH terms

  • Blood Platelets / pathology
  • Child
  • Chromosomes, Human, Pair 22 / genetics
  • DNA Mutational Analysis
  • Diagnosis, Differential
  • Genes, Dominant / genetics
  • Genetic Carrier Screening
  • Humans
  • Microscopy, Fluorescence
  • Molecular Motor Proteins / genetics*
  • Myosin Heavy Chains / genetics*
  • Pedigree
  • Software Design
  • Syndrome
  • Thrombocytopenia / diagnosis*
  • Thrombocytopenia / genetics*
  • Thrombocytopenia / pathology

Substances

  • MYH9 protein, human
  • Molecular Motor Proteins
  • Myosin Heavy Chains