MYH9-related disease: it does exist, may be more frequent than you think and requires specific therapy

Abstract

In this issue of ckj, Tabibzadeh et al. report one of the largest series of patients with MYH9 mutations and kidney disease. The cardinal manifestation of MYH9-related disease is thrombocytopenia with giant platelets. The population frequency of pathogenic MYH9 mutations may be at least 1 in 20 000. The literature abounds in misdiagnosed cases treated for idiopathic thrombocytopenic purpura with immune suppressants and even splenectomy. Additional manifestations include neurosensorial deafness and proteinuric and hematuric progressive kidney disease (at some point, it was called Alport syndrome with macrothrombocytopenia), leucocyte inclusions, cataracts and liver enzyme abnormalities, resulting in different names for different manifestation combinations (MATINS, May–Hegglin anomaly, Fechtner, Epstein and Sebastian syndromes, and deafness AD 17). The penetrance and severity of kidney disease are very variable, which may obscure the autosomal dominant inheritance. A correct diagnosis will both preclude unnecessary and potentially dangerous therapeutic interventions and allow genetic counselling and adequate treatment. Morphological erythrocyte, granulocyte and platelet abnormalities may allow the future development of high-throughput screening techniques adapted to clinical peripheral blood flow cytometers.

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“…The MYH9 gene is involved in synthesizing a protein called myosin-9 which is one subunit of the myosin IIA protein. The MYH9-related disorder includes thrombocytopenia, hearing loss, kidney disease, and cataracts [ 70 ]. Mutations in the MYH9 gene lead to a genetic condition known as MYH9-related thrombocytopenia (MYH9RD) which is characterized by the presence of large but lesser platelets, results in bleeding in the body or the skin [ 71 ].…”

Moyamoya-like vasculopathy associated to MYH9-related thrombocytopenia manifested by multiple cerebral ischemic lesions: a case report

“…Each disorder of this group is characterized, beside thrombocytopenia, by a combination of clinical and laboratory findings like granulocyte inclusion bodies, hypoacusia, glomerular nephropathy, and cataract [ 16 ]. In our patient, nephritis and cataract were excluded by clinical and ancillary laboratory tests, and leukocyte inclusion bodies were absent.…”

“…In our patient, nephritis and cataract were excluded by clinical and ancillary laboratory tests, and leukocyte inclusion bodies were absent. She presented only hearing loss, as some genetic variants are associated mainly with sensorineural hypoacusia secondary to cochlear-saccular degeneration [ 16 ].…”

Hypertensive nephropathy: a major roadblock hindering the advance of precision nephrology

“…This is the title of an editorial comment published in 2008 that could have been the epitaph of hypertensive nephropathy [ 13 ]. While the reason to claim the end of the concept of hypertension-associated kidney disease was partially wrong (the high incidence of CKD in African-Americans had been linked to MYH9 variants, but while MYH9 variants may cause kidney disease, they are not the cause of the increased risk of CKD in African-Americans [ 14 ]), it did point in the right direction: 2 years later, in 2010, the high incidence of CKD (and of hypertensive CKD) in African-Americans was pinpointed to risk variants in apolipoprotein 1 ( APOL1 ) [ 15 , 16 ]. Indeed, APOL1 risk variants underlie the high risk of African-Americans for human immunodeficiency virus–associated nephropathy and other nephropathies [ 17 ].…”