A rare inherited platelet disorder characterised by macrothrombocytopenia, defective platelet adhesion, and a mild to severe bleeding tendency.

Epidemiology
Bernard–Soulier syndrome is a very rare disorder, with an estimated prevalence of less than 1 per 1,000,000 individuals. Both sexes are equally affected. The condition is more frequently reported in populations with higher rates of consanguinity.

Clinical description
Bleeding manifestations usually begin in childhood and are predominantly mucocutaneous. Common symptoms include easy bruising, epistaxis, gingival bleeding, menorrhagia, and excessive bleeding following trauma, dental procedures, or surgery.
Bleeding severity is variable, ranging from mild to severe. Thrombocytopenia with abnormally large platelets (macrothrombocytes) is a characteristic feature. Joint and deep muscle bleeding are uncommon.

Etiology
Bernard–Soulier syndrome is caused by pathogenic variants in the GP1BA, GP1BB, or GP9 genes, which encode components of the platelet glycoprotein Ib/IX/V complex. This receptor complex is essential for platelet adhesion to von Willebrand factor at sites of vascular injury. Defective or absent receptor function results in impaired primary haemostasis.

Diagnosis is based on:

Thrombocytopenia with large platelets on peripheral blood smear
Absent or markedly reduced ristocetin-induced platelet agglutination that does not correct with the addition of normal plasma
Normal or near-normal coagulation tests
Flow cytometry demonstrating reduced or absent glycoprotein Ib/IX/V expression can confirm the diagnosis. Genetic testing may be used for confirmation and family studies.

Differential diagnosis
Differential diagnoses include:
Immune thrombocytopenia
Other inherited platelet function disorders
Type 2B von Willebrand disease
MYH9-related disorders
Careful laboratory evaluation is required to avoid misdiagnosis.

Genetic counseling
Inheritance is autosomal recessive. Genetic counselling is recommended for affected individuals and their families. Carrier couples have a 25% risk of having an affected child with each pregnancy.