From the Guidelines
Bernard Soulier Syndrome is inherited in an autosomal recessive pattern, meaning an individual must inherit two defective copies of the gene to develop the condition. This pattern of inheritance implies that parents who are carriers have one normal copy and one defective copy of the gene, typically showing no symptoms themselves. When both parents are carriers, there is a 25% chance with each pregnancy that their child will inherit two defective copies and develop Bernard Soulier Syndrome. The genetic defect involves mutations in the genes encoding glycoprotein Ib-IX-V complex (GP1BA, GP1BB, or GP9), which is essential for platelet adhesion to blood vessel walls 1.
Key Points
- The condition results from mutations in the genes GP1BA, GP1BB, or GP9, leading to defective platelet adhesion to blood vessel walls.
- Affected individuals have giant platelets that are unable to adhere properly to damaged blood vessels, resulting in prolonged bleeding time and increased risk of hemorrhage.
- Genetic counseling is recommended for affected individuals and their families to understand inheritance patterns and reproductive options.
- The diagnosis of inherited platelet function disorders, including Bernard Soulier Syndrome, can be challenging due to the lack of standardized approaches and diagnostic criteria 1.
Clinical Implications
The autosomal recessive inheritance pattern of Bernard Soulier Syndrome has significant implications for genetic counseling and family planning. Affected individuals and their families should be aware of the risks of transmitting the condition to their offspring. Additionally, the diagnosis and management of Bernard Soulier Syndrome require a comprehensive approach, including laboratory tests and clinical evaluation to assess platelet function and bleeding risk 1.
From the Research
Inheritance Pattern of Bernard-Soulier Syndrome
- The inheritance pattern of Bernard-Soulier syndrome (BSS) is autosomal recessive 2, 3, 4, 5.
- This means that the syndrome is transmitted as an autosomal recessive trait, where an individual must inherit two copies of the mutated gene (one from each parent) to express the condition.
- The autosomal recessive inheritance pattern is supported by the fact that the frequency of the disorder is increased in populations where consanguineous marriages are common 5.
- The genetic defect responsible for BSS is a deficiency or dysfunction of the glycoprotein GPIb-V-IX complex, which is a platelet-restricted multisubunit receptor required for normal primary hemostasis 2.
Genetic Basis of Bernard-Soulier Syndrome
- The genes coding for the four subunits of the GPIb-V-IX complex, GPIBA, GPIBB, GP5, and GP9, map to different chromosomes 2.
- Defects have been identified in GPIBA, GPIBB, and GP9, but not in GP5 2.
- Genetic analyses of the disease-related genes may help to gain more insights regarding the phenotype/genotype correlation 5.
- Different mutations in the GP1BB and GP9 genes have been associated with varying severity of the bleeding phenotype in patients with BSS 5.