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Bernard Soulier syndrome(BSS)

MedGen UID:
2212
Concept ID:
C0005129
Disease or Syndrome
Synonyms: BLEEDING DISORDER, PLATELET-TYPE, 1; BSS; Giant platelet disease; Giant platelet syndrome; GLYCOPROTEIN Ib, PLATELET, DEFICIENCY OF; Hemorrhagiparous thrombocytic dystrophy; Platelet glycoprotein 1b, deficiency of; PLATELET GLYCOPROTEIN Ib DEFICIENCY; Von Willebrand factor receptor deficiency
SNOMED CT: Bernard-Soulier syndrome (54569005); Giant platelet syndrome (234478007); Bernard Soulier syndrome (54569005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Genes (locations): GP1BA (17p13.2); GP1BB (22q11.21); GP9 (3q21.3)
 
Monarch Initiative: MONDO:0009276
OMIM®: 231200
Orphanet: ORPHA274

Definition

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]

Additional description

From MedlinePlus Genetics
Bernard-Soulier syndrome is a bleeding disorder associated with abnormal platelets, which are blood cells involved in blood clotting. In affected individuals, platelets are unusually large and fewer in number than usual (a combination known as macrothrombocytopenia). People with Bernard-Soulier syndrome tend to bruise easily and have an increased risk of nosebleeds (epistaxis). They may also experience abnormally heavy or prolonged bleeding following minor injury or surgery or even without trauma (spontaneous bleeding). Rarely, bleeding under the skin causes tiny red or purple spots on the skin called petechiae. Women with Bernard-Soulier syndrome often have heavy or prolonged menstrual bleeding (menorrhagia).  https://medlineplus.gov/genetics/condition/bernard-soulier-syndrome

Clinical features

From HPO
Gastrointestinal hemorrhage
MedGen UID:
8971
Concept ID:
C0017181
Pathologic Function
Hemorrhage affecting the gastrointestinal tract.
Epistaxis
MedGen UID:
4996
Concept ID:
C0014591
Pathologic Function
Epistaxis, or nosebleed, refers to a hemorrhage localized in the nose.
Gingival bleeding
MedGen UID:
42218
Concept ID:
C0017565
Pathologic Function
Hemorrhage affecting the gingiva.
Menorrhagia
MedGen UID:
44358
Concept ID:
C0025323
Pathologic Function
Prolonged and excessive menses at regular intervals in excess of 80 mL or lasting longer than 7 days.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Prolonged bleeding time
MedGen UID:
56231
Concept ID:
C0151529
Finding
Prolongation of the time taken for a standardized skin cut of fixed depth and length to stop bleeding.
Giant platelets
MedGen UID:
137700
Concept ID:
C0333864
Finding
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).
Abnormal bleeding
MedGen UID:
264316
Concept ID:
C1458140
Pathologic Function
An abnormal susceptibility to bleeding, often referred to as a bleeding diathesis. A bleeding diathesis may be related to vascular, platelet and coagulation defects.
Prolonged bleeding after dental extraction
MedGen UID:
369536
Concept ID:
C1969572
Pathologic Function
Prolonged bleeding post dental extraction sufficient to require medical intervention.
Macrothrombocytopenia
MedGen UID:
414334
Concept ID:
C2751260
Disease or Syndrome
Prolonged bleeding after surgery
MedGen UID:
867284
Concept ID:
C4021646
Pathologic Function
Bleeding that persists longer than the normal time following a surgical procedure.
Impaired ristocetin-induced platelet aggregation
MedGen UID:
868749
Concept ID:
C4023154
Pathologic Function
Abnormal response to ristocetin as manifested by reduced or lacking aggregation of platelets upon addition of ristocetin.
Purpura
MedGen UID:
19584
Concept ID:
C0034150
Disease or Syndrome
Purpura (from Latin

Professional guidelines

PubMed

Shapiro A
Thromb Res 2020 Dec;196:590-602. Epub 2019 Jul 19 doi: 10.1016/j.thromres.2019.07.014. PMID: 31420204
Dupuis A, Gachet C
Transfus Clin Biol 2018 Sep;25(3):228-235. Epub 2018 Aug 1 doi: 10.1016/j.tracli.2018.07.003. PMID: 30077511
Seligsohn U
Haemophilia 2012 Jul;18 Suppl 4:161-5. doi: 10.1111/j.1365-2516.2012.02842.x. PMID: 22726101

Recent clinical studies

Etiology

Thakar S, Gabarin N, Gupta A, Radford M, Warkentin TE, Arnold DM
Transfus Med Rev 2021 Jul;35(3):22-28. Epub 2021 Jun 15 doi: 10.1016/j.tmrv.2021.06.001. PMID: 34332828
Nurden AT, Nurden P
Haematologica 2020 Aug;105(8):2004-2019. Epub 2020 Jun 11 doi: 10.3324/haematol.2019.233197. PMID: 32527953Free PMC Article
Shapiro A
Thromb Res 2020 Dec;196:590-602. Epub 2019 Jul 19 doi: 10.1016/j.thromres.2019.07.014. PMID: 31420204
Seligsohn U
Haemophilia 2012 Jul;18 Suppl 4:161-5. doi: 10.1111/j.1365-2516.2012.02842.x. PMID: 22726101
Blanchette VS, Sparling C, Turner C
Baillieres Clin Haematol 1991 Apr;4(2):291-332. doi: 10.1016/s0950-3536(05)80162-3. PMID: 1912663

Diagnosis

Nurden AT, Nurden P
Haematologica 2020 Aug;105(8):2004-2019. Epub 2020 Jun 11 doi: 10.3324/haematol.2019.233197. PMID: 32527953Free PMC Article
Sandrock-Lang K, Wentzell R, Santoso S, Zieger B
Hamostaseologie 2016 Aug 3;36(3):178-86. Epub 2015 Feb 24 doi: 10.5482/HAMO-14-11-0067. PMID: 25707719
Balduini CL, Savoia A, Seri M
J Thromb Haemost 2013 Jun;11(6):1006-19. doi: 10.1111/jth.12196. PMID: 23510089
Nurden AT, Freson K, Seligsohn U
Haemophilia 2012 Jul;18 Suppl 4:154-60. doi: 10.1111/j.1365-2516.2012.02856.x. PMID: 22726100
Blanchette VS, Sparling C, Turner C
Baillieres Clin Haematol 1991 Apr;4(2):291-332. doi: 10.1016/s0950-3536(05)80162-3. PMID: 1912663

Therapy

Lee A, Poon MC
Transfus Apher Sci 2018 Aug;57(4):494-501. Epub 2018 Jul 19 doi: 10.1016/j.transci.2018.07.010. PMID: 30031712
Rodeghiero F, Pecci A, Balduini CL
J Thromb Haemost 2018 Sep;16(9):1700-1710. Epub 2018 Jul 27 doi: 10.1111/jth.14217. PMID: 29956472
Seligsohn U
Haemophilia 2012 Jul;18 Suppl 4:161-5. doi: 10.1111/j.1365-2516.2012.02842.x. PMID: 22726101
Bennett JS, Kolodziej MA
Dis Mon 1992 Aug;38(8):577-631. PMID: 1321709
Blanchette VS, Sparling C, Turner C
Baillieres Clin Haematol 1991 Apr;4(2):291-332. doi: 10.1016/s0950-3536(05)80162-3. PMID: 1912663

Prognosis

Bannow BS, Konkle BA
Transfus Med Rev 2018 Oct;32(4):237-243. Epub 2018 Jul 12 doi: 10.1016/j.tmrv.2018.06.003. PMID: 30097224
Noris P, Balduini CL
Haematologica 2015 Feb;100(2):145-8. doi: 10.3324/haematol.2014.122549. PMID: 25638803Free PMC Article
Roberts I, Stanworth S, Murray NA
Blood Rev 2008 Jul;22(4):173-86. Epub 2008 Apr 22 doi: 10.1016/j.blre.2008.03.004. PMID: 18433954
Freson K, Labarque V, Thys C, Wittevrongel C, Geet CV
Eur J Pediatr 2007 Dec;166(12):1203-10. Epub 2007 Jul 10 doi: 10.1007/s00431-007-0543-7. PMID: 17619901Free PMC Article
Lanza F
Orphanet J Rare Dis 2006 Nov 16;1:46. doi: 10.1186/1750-1172-1-46. PMID: 17109744Free PMC Article

Clinical prediction guides

Mekchay P, Ittiwut C, Ittiwut R, Akkawat B, Le Grand SM, Leela-Adisorn N, Muanpetch S, Khovidhunkit W, Sosothikul D, Shotelersuk V, Suphapeetiporn K, Rojnuckarin P
Medicine (Baltimore) 2020 Nov 20;99(47):e23275. doi: 10.1097/MD.0000000000023275. PMID: 33217855Free PMC Article
Shapiro A
Thromb Res 2020 Dec;196:590-602. Epub 2019 Jul 19 doi: 10.1016/j.thromres.2019.07.014. PMID: 31420204
Bragadottir G, Birgisdottir ER, Gudmundsdottir BR, Hilmarsdottir B, Vidarsson B, Magnusson MK, Larsen OH, Sorensen B, Ingerslev J, Onundarson PT
Am J Hematol 2015 Feb;90(2):149-55. Epub 2014 Nov 24 doi: 10.1002/ajh.23891. PMID: 25370924
Kulkarni BP, Nair SB, Vijapurkar M, Mota L, Shanbhag S, Ali S, Shetty SD, Ghosh K
PLoS One 2014;9(9):e108683. Epub 2014 Oct 2 doi: 10.1371/journal.pone.0108683. PMID: 25275492Free PMC Article
Roberts I, Stanworth S, Murray NA
Blood Rev 2008 Jul;22(4):173-86. Epub 2008 Apr 22 doi: 10.1016/j.blre.2008.03.004. PMID: 18433954

Recent systematic reviews

Punt MC, Schuitema PCE, Bloemenkamp KWM, Kremer Hovinga ICL, van Galen KPM
Haemophilia 2020 Mar;26(2):216-227. Epub 2020 Jan 31 doi: 10.1111/hae.13927. PMID: 32004416Free PMC Article
Kulkarni BP, Nair SB, Vijapurkar M, Mota L, Shanbhag S, Ali S, Shetty SD, Ghosh K
PLoS One 2014;9(9):e108683. Epub 2014 Oct 2 doi: 10.1371/journal.pone.0108683. PMID: 25275492Free PMC Article
Peitsidis P, Datta T, Pafilis I, Otomewo O, Tuddenham EG, Kadir RA
Haemophilia 2010 Jul 1;16(4):584-91. Epub 2010 Jan 12 doi: 10.1111/j.1365-2516.2009.02137.x. PMID: 20070385

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