[Clinical and genetic features of seven children with MYH9-related disease]

Objective: To summarize and analyze of the clinical and genetic characteristics of children with nonmuscle myosin heavy chain 9 (MYH9)-related disease (MYH9-RD). Methods: To screen the patients who were first diagnosed as "chronic/refractory immune thrombocytopenia (ITP) " from April 2016 to May 2019 in Beijing Children's Hospital by genetic and clinical examinations, then the clinical manifestation, laboratory examination and genetics results of 7 children diagnosed with MYH9-RD were collected and summarized retrospectively. Results: Among 7 children diagnosed with MYH9-RD, 3 were males and 4 females. The age of onset was 1.25 (0.41-6.16) years. The course of disease was 2.16 (0.41-8.59) years. The automatic platelet count was (9 (5-30))×10⁹/L. All the cases were found with giant platelets under microscope,and the manual platelet count was (70 (30-100))×10⁹/L. Four cases had skin hemorrhage or epistaxis and 3 cases had no bleeding. All 7 patients had received first-or second-line therapy of ITP, of whom 1 case received splenic embolization, and all the treatments mentioned above were ineffective. Finally, it was confirmed that all 7 patients had heterozygous missense mutations of MYH9 gene by next generation sequencing (NGS), including 2 pedigrees and 5 sporadic cases. Four sporadic mutations occurred in N-terminal globular head domain (HD), and 1 sporadic case with p.D1424N mutations occurred in the C-terminal tail domain (TD). One of the pedigrees also had p.D1424N mutation. The other familial case had a novel variant with one missense variant p.A44D caused by the c.131C>A transition. One of the two p.R702 mutations had kidney damage, and several relatives of the new p.A44D mutations had deafness. Conclusions: In this study, the spontaneous mutations of seven MYH9-RD were common, and all patients were misdiagnosed as ITP, whereas the bleeding was mild and immunotherapy was ineffective. The suspected disease can be identified earlier by manual visual platelet volume and count, which can be confirmed by genetic testing. It is more important to monitor the development of other organs damage instead of thrombocytopenia. For cases with p.R702 mutations the doctor should be aware of kidney damage, and for the cases with novel mutations p.A44D the doctor should be aware of hearing loss.