MYH9 Related Platelet Disorders – Often Unknown and Misdiagnosed

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.

Zusammenfassung

MYH9-assoziierte Erkrankungen gehören zu den angeborenen Makrothrombozytopenien. Sie sind verursacht durch Veränderungen im MYH9-Gen auf dem langen Arm von Chromosom 22. Heterozygote Mutationen in diesem Gen führen zu den 4 unterschiedlichen Syndromen: May-Hegglin-Anomalie, Epstein-Syndrom, Fechtner-Syndrom und Sebastian-Platelet-Syndrom. Klinisch gemeinsam ist den 4 Syndromen eine Makrothrombozytopenie mit einer leichter Blutungsneigung. Abhängig von Lage und Art der Mutation können sich bei den Patienten zusätzlich Nierenversagen, Hörverlust im Hochtonbereich und Katarakt manifestieren. Die Erkrankung scheint deutlich häufiger zu sein, als bislang angenommen. Eine MYH9-assoziierte Erkrankung sollte bei allen Patienten mit chronischer Thrombozytopenie und vergrößerten Thrombozyten ausgeschlossen werden. Das größte Risiko ist derzeit eine nebenwirkungsreiche und dabei ineffektive Behandlung auf Grundlage der Fehldiagnose „Autoimmunthrombozytopenie”. Die Arbeit zeigt einen Weg zur rationellen Diagnostik dieser Erkrankung, diskutiert verschiedene Behandlungsmöglichkeitenund beschreibt klinische Manifestation und molekulare Pathogenese der MYH9-assoziierten Thrombozytopenie.

MYH9 - platelet - ITP - macrothrombocytopenia - May Hegglin anomaly - Epstein syndrome - Fechtner syndrome - Sebastian platelet syndrome

MYH9 - Thrombozyten - ITP - Makrothrombozytopenie - Epstein-Syndrom

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