Frequently Delayed Diagnosis and Misdiagnosis in MYH9-related Disorders: Data from Genetically Confirmed Cases of Korean Patients

MYH9-related disorders (MYH9RD) are autosomal-dominant disorders characterized by macrothrombocytopenia with or without leukocyte inclusion bodies or extra-hematological features, such as sensorineural deafness and renal impairment. MYH9RD can be misdiagnosed as an acquired form of thrombocytopenia including immune thrombocytopenic purpura (ITP). This leads to delayed diagnosis or administration of ineffective treatment. In the present study, we investigated the clinical and molecular characteristics of five unrelated Korean patients with MYH9RD and their family members, from four institutions. We reviewed clinical and laboratory data including extra-hematological manifestations. MYH9 pathogenic variants were detected by direct sequencing in all probands and the affected family members (N=10): two probands with c.5521G>A (p.Glu1841Lys) and one proband each with c.99G>T (p.Trp33Cys), c.287C>T (p.Ser96Leu), and c.3493C>T (p.Arg1165Cys). All patients had macrothrombocytopenia. Only the proband with Ser96Leu had extra-hematological manifestations. Past history revealed that two patients had been misdiagnosed with ITP and one of them had received a splenectomy. We validated the frequency of misdiagnosis (~20%) and genotype-phenotype correlations through a comprehensive review of previously reported cases of MYH9RD in Korea. It is important to suspect MYH9RD in patients with thrombocytopenia, and timely identification of macrothrombocytopenia and MYH9 pathogenic variants is required for early and accurate diagnosis of MYH9RD.

Giant platelet syndrome / 소아과

Giant platelet syndrome is a group of unique disorders characterized by the presence of abnormally large platelets, and usually accompanied by thrombocytopenia. Most cases of giant platelets are encountered in idiopathic thrombocytopenic purpura(ITP). In contrast, inherited giant platelet disorders, a group of heterogeneous diseases, are rare. Bernard-Soulier syndrome and its variants, and MYH9 related diseases have been defined at the molecular level. Abnormalities in transcription factors are implicated in a couple of macrothrombocytopenia syndromes. However, the molecular defects are unknown in gray platelet syndrome. It is important to make a proper diagnosis of congenital macrothrombocytopenia to avoid unnecessary medications and potentially dangerous treatment for presumed ITP.

MYH9-related Disorder in a Family: Autosomal Dominant Epstein Giant Platelet Syndrome / 대한소아혈액종양학회지

The term MYH9-related disorders indicates a group of autosomal dominant illnesses, formerly known as May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome and Epstein syndrome, caused by mutations of MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA (NMMHC-IIA). We experienced a family with macrothrombocytopenia without leukocyte inclusion. A 5-year-old girl was found to have macrothrombocytopenia incidentally. Her father also had macrothromtocytopenia, but had been suffering from hearing loss and chronic renal failure. Meticulous search by light and electron microscopy failed to detect leukocyte inclusions. To our knowledge, these cases seem to be the first description of autosomal dominant Epstein giant platelet syndrome in Korea.

A Nonsense C5797T (R1933X) Mutation of MYH9 Gene in a Family with May-Hegglin Anomaly / 대한혈액학회지

May-Hegglin anomaly (MHA) is an autosomal dominant disorder characterized by macrothrombocytopenia and leukocyte inclusions. In 1992, we reported the first Korean case of MHA family. Again, in this family, we identified a nonsense C5797T mutation (R1933X) in the MYH9 gene, encoding non-muscle myosin heavy chain A. To the best of our knowledge, our genetic study in this MHA family is the first report of mutation resulting in the truncation of 28 of 34 amino acids of the carboxy-terminal tailpiece of the myosin heavy chain in Korea.