SNP Shot: Genomic Insights

MYH9-related disorder is characterized by a range of potential symptoms, including bleeding abnormalities, hearing impairment, kidney (renal) dysfunction, and clouding of the eye's lens (cataracts).

Bleeding issues in individuals with MYH9-related disorder stem from thrombocytopenia, a condition marked by a reduced number of platelets in the bloodstream. Platelets are essential for blood clot formation. Consequently, individuals with this disorder often experience easy bruising, and women may have excessively heavy menstrual bleeding (menorrhagia). The platelets in affected individuals are abnormally large, hindering their ability to navigate small blood vessels such as capillaries. This results in an even lower platelet count in these vessels, further impairing blood clotting.

Some individuals with MYH9-related disorder experience hearing loss due to inner ear abnormalities (sensorineural hearing loss). This hearing loss may be present at birth or develop at any point up to late adulthood.

Renal disease, affecting an estimated 30 to 70 percent of those with MYH9-related disorder, typically emerges in early adulthood. The initial indication is usually the presence of protein or blood in the urine. This renal disease primarily impacts the glomeruli, tiny blood vessel clusters responsible for filtering waste from the blood. The resulting kidney damage can progress to kidney failure and end-stage renal disease (ESRD).

Some affected individuals develop cataracts during early adulthood, which worsen progressively over time.

Not all individuals with MYH9-related disorder exhibit all of the major symptoms. However, thrombocytopenia and enlarged platelets are universally present. Hearing loss and renal disease are also common manifestations. Cataracts are the least frequently observed symptom.

Historically, MYH9-related disorder was classified as four distinct disorders: May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, and Sebastian syndrome. These conditions all shared the characteristics of thrombocytopenia and enlarged platelets, and were differentiated by varying combinations of hearing loss, renal disease, and cataracts. Upon the discovery of a shared genetic origin, these four conditions were consolidated and renamed MYH9-related disorder.

Inheritance:

The inheritance pattern of this condition is autosomal dominant. This means that a single copy of the mutated gene in each cell is sufficient to cause the disorder. In the majority of cases, an affected individual inherits the mutation from a parent who also has the disorder. However, approximately 30 percent of cases arise from new, spontaneous mutations in the gene, occurring in individuals with no family history of the condition.