MedGen

MYH9-related disease (MYH9-RD) is characterized in all affected individuals by hematologic features present from birth consisting of platelet macrocytosis (i.e., >40% of platelets larger than 3.9 µm in diameter), thrombocytopenia (platelet count <150 x 109/L), and aggregates of the MYH9 protein in the cytoplasm of neutrophil granulocytes. Most affected individuals develop one or more additional extrahematologic manifestations of the disease over their lifetime, including sensorineural hearing loss, renal disease (manifesting initially as glomerular nephropathy), presenile cataracts, and/or elevation of liver enzymes. [from GeneReviews]

Bernard-Soulier syndrome is an autosomal recessive bleeding disorder caused by a defect in or deficiency of the platelet membrane von Willebrand factor (VWF; 613160) receptor complex, glycoprotein Ib (GP Ib). GP Ib is composed of 4 subunits encoded by 4 separate genes: GP1BA, GP1BB, GP9, and GP5 (173511). Genetic Heterogeneity of Platelet-Type Bleeding Disorders Inherited platelet disorders are a heterogeneous group of bleeding disorders affecting platelet number, function, or both. Functional defects can involve platelet receptors, signaling pathways, cytoskeletal proteins, granule contents, activation, or aggregation (review by Cox et al., 2011 and Nurden and Nurden, 2011). Platelet-type bleeding disorders include Bernard-Soulier syndrome (BDPLT1); Glanzmann thrombasthenia (BDPLT2; 273800), caused by mutation in the ITGA2B (607759) or ITGB3 (173470) gene; pseudo-von Willebrand disease (BDPLT3; 177820), caused by mutation in the GP1BA gene (606672); gray platelet syndrome (BDPLT4; 139090), caused by mutation in the NBEAL2 gene (614169); Quebec platelet disorder (BDPLT5; 601709), caused by tandem duplication of the PLAU gene (191840); May-Hegglin anomaly (BDPLT6; 155100), caused by mutation in the MYH9 gene (160775); Scott syndrome (BDPLT7; 262890), caused by mutation in the TMEM16F gene (608663); BDPLT8 (609821), caused by mutation in the P2RY12 gene (600515); BDPLT9 (614200), associated with deficiency of the glycoprotein Ia/IIa receptor (see ITGA2; 192974); glycoprotein IV deficiency (BDPLT10; 608404), caused by mutation in the CD36 gene (173510); BDPLT11 (614201), caused by mutation in the GP6 gene (605546); BDPLT12 (605735), associated with a deficiency of platelet COX1 (176805); susceptibility to BDPLT13 (614009), caused by mutation in the TBXA2R gene (188070); BDPLT14 (614158), associated with deficiency of thromboxane synthetase (TBXAS1; 274180); BDPLT15 (615193), caused by mutation in the ACTN1 gene (102575); BDPLT16 (187800), caused by mutation in the ITGA2B (607759) or ITGB3 (173470) gene; BDPLT17 (187900), caused by mutation in the GFI1B gene (604383); BDPLT18 (615888), caused by mutation in the RASGRP2 gene (605577); BDPLT19 (616176), caused by mutation in the PRKACG gene (176893); BDPLT20 (616913), caused by mutation in the SLFN14 gene (614958); BDPLT21 (617443), caused by mutation in the FLI1 gene (193067); BDPLT22 (618462), caused by mutation in the EPHB2 gene (600997); BDPLT23 (619267), caused by mutation in the ITGB3 gene (173470); BDPLT24 (619271), caused by mutation in the ITGB3 gene (173470); and BDPLT25 (620486), caused by mutation in the TPM4 gene (600317). See reviews by Rao (2003), Cox et al. (2011), and Nurden and Nurden (2011). For a discussion of the genetic heterogeneity of hereditary thrombocytopenia, see THC1 (313900). [from OMIM]

Sitosterolemia is characterized by: Hypercholesterolemia (especially in children) which (1) shows an unexpected significant lowering of plasma cholesterol level in response to low-fat diet modification or to bile acid sequestrant therapy; or (2) does not respond to statin therapy; Tendon xanthomas or tuberous (i.e., planar) xanthomas that can occur in childhood and in unusual locations (heels, knees, elbows, and buttocks); Premature atherosclerosis, which can lead to angina, aortic valve involvement, myocardial infarction, and sudden death; Hemolytic anemia, abnormally shaped erythrocytes (stomatocytes), and large platelets (macrothrombocytopenia). On occasion, the abnormal hematologic findings may be the initial presentation or the only clinical feature of this disorder. Arthritis, arthralgias, and splenomegaly may sometimes be seen and one study has concluded that "idiopathic" liver disease could be undiagnosed sitosterolemia. The clinical spectrum of sitosterolemia is probably not fully appreciated due to underdiagnosis and the fact that the phenotype in infants is likely to be highly dependent on diet. [from GeneReviews]

An extremely rare form of carbohydrate deficient glycoprotein syndrome with, in the few cases reported to date, variable signs including microcephaly, growth retardation, psychomotor retardation and facial dysmorphism. [from SNOMEDCT_US]

Platelet-type bleeding disorder-16 (BDPLT16) is an autosomal dominant form of congenital macrothrombocytopenia associated with platelet anisocytosis. It is a disorder of platelet production. Affected individuals may have no or only mildly increased bleeding tendency. In vitro studies show mild platelet functional abnormalities (summary by Kunishima et al., 2011 and Nurden et al., 2011). Genetic Heterogeneity of Glanzmann Thrombasthenia-like with Macrothromocytopenia See BDPLT24 (619271), caused by mutation in the ITGB3 gene (173470) on chromosome 17q21.32. Together the ITGB2B and ITBG3 genes form an integrin, known as platelet glycoprotein GPIIb/III, that is expressed on platelets. [from OMIM]

An autosomal dominant inherited condition caused by mutations in the lamin B receptor gene. It is characterized by defects in the neutrophil lobulation, resulting in the presence of dumbbell-shaped neutrophils with bilobed nuclei in the peripheral blood smear. [from NCI]

Any inherited bleeding disorder, platelet-type in which the cause of the disease is a mutation in the CD36 gene. [from MONDO]

Giant platelets are larger than 7 micrometers and usually 10 to 20 micrometers. The term giant platelet is used when the platelet is larger than the size of the average red cell in the field. (Description adapted from College of American Pathologists, Hematology Manual, 1998). [from HPO]