MedGen

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]

Glanzmann thrombasthenia is a bleeding disorder that is characterized by prolonged or spontaneous bleeding starting from birth. People with Glanzmann thrombasthenia tend to bruise easily, have frequent nosebleeds (epistaxis), and may bleed from the gums. They may also develop red or purple spots on the skin caused by bleeding underneath the skin (petechiae) or swelling caused by bleeding within tissues (hematoma). Glanzmann thrombasthenia can also cause prolonged bleeding following injury, trauma, or surgery (including dental work). Women with this condition can have prolonged and sometimes abnormally heavy menstrual bleeding. Affected women also have an increased risk of excessive blood loss during pregnancy and childbirth.

About a quarter of individuals with Glanzmann thrombasthenia have bleeding in the gastrointestinal tract, which often occurs later in life. Rarely, affected individuals have bleeding inside the skull (intracranial hemorrhage) or joints (hemarthrosis).

The severity and frequency of the bleeding episodes in Glanzmann thrombasthenia can vary greatly among affected individuals, even in the same family. Spontaneous bleeding tends to become less frequent with age. [from MedlinePlus Genetics]

Autosomal dominant Bernard-Soulier syndrome type A2 (BSSA2) is characterized by chronic macrothrombocytopenia with mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count. When present, clinical findings include excessive ecchymoses, frequent epistaxis, gingival bleeding, prolonged menstrual periods, or prolonged bleeding after tooth extraction (Savoia et al., 2001). Genetic Heterogeneity of Bernard-Soulier Syndrome Homozygous or compound heterozygous mutations in the GP1BA gene cause classic autosomal recessive Bernard-Soulier syndrome (BSSA1; 231200). [from OMIM]

Platelet-type bleeding disorder-11 is an autosomal recessive mild to moderate bleeding disorder caused by defective platelet activation and aggregation in response to collagen (summary by Dumont et al., 2009). [from OMIM]

Platelet-type bleeding disorder-24 (BDPLT24) 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). For a discussion of genetic heterogeneity of Glanzmann thrombasthenia-like with macrothrombocytopenia, see 187800. [from OMIM]

Glanzmann thrombasthenia-2 (GT2) is an autosomal recessive bleeding disorder characterized by failure of platelet aggregation and by absent or diminished clot retraction. The abnormalities are related to quantitative or qualitative abnormalities of the GPIIb (607759)/IIIa platelet surface fibrinogen receptor complex resulting from mutations in the GPIIIa gene (Rosenberg et al., 1997). For a general phenotypic description and a discussion of genetic heterogeneity of Glanzmann thrombasthenia, see 273800. [from OMIM]

Platelet-type bleeding disorder-22 (BDPLT22) is an autosomal recessive bleeding disorder resulting from impaired platelet aggregation due to intracellular signaling defects. Patients present in the first decade with spontaneous subcutaneous bleeding and excessive bleeding after minor injuries. Platelet counts are usually normal, although platelets show abnormal morphology (summary by Berrou et al., 2018). [from OMIM]

Thrombocytopenia-7 (THC7) is an autosomal dominant disorder characterized by reduced peripheral platelet count. The expression and severity of the disorder is highly variable: some patients have no bleeding symptoms, whereas other have recurrent petechiae, epistaxis, or more severe bleeding episodes. A common finding is decreased alpha-granules in the platelets. There are variable findings on light and electron microscopic analysis: some patients have normal platelet morphology, whereas others show abnormal platelet morphology with cytoskeletal defects. Flow cytometric studies may show reduced expression of platelet membrane glycoproteins and activation markers (summary by Lentaigne et al., 2019 and Leinoe et al., 2021). For a general phenotypic description and a discussion of genetic heterogeneity of thrombocytopenia, see 313900. [from OMIM]

Abnormal response to ristocetin as manifested by reduced or lacking aggregation of platelets upon addition of ristocetin. [from HPO]