Bernard-Soulier syndrome

Bernard-Soulier syndrome is an inherited bleeding disorder that affects how platelets stick together to form a clot. It results from changes in one of three genes—GP1BA, GP1BB, or GP9—that encode parts of the platelet glycoprotein Ib-IX-V receptor, the docking site for von Willebrand factor during clot formation. Because this receptor is missing or reduced, affected individuals have fewer and unusually large platelets that do not function normally, leading to easy bleeding. The condition is very rare, affecting fewer than one in one million people worldwide and occurring in both males and females. Severity and symptoms vary widely between individuals.

The hallmark features are a low platelet count combined with unusually large ("giant") platelets and the complete absence of platelet clumping in the laboratory test that uses the agent ristocetin. Clinically, many people first come to attention because of mucocutaneous bleeding such as easy bruising, frequent nosebleeds, or gum bleeding. Others are diagnosed after prolonged bleeding following dental work or surgery. Heavy menstrual bleeding is common among affected women, and some individuals experience gastrointestinal bleeding or visible blood in the urine. Petechiae and spontaneous skin bruises can occur, and a subset of individuals develop deep bruises or soft-tissue hematomas. Not all individuals experience all features, and the frequency and severity of bleeding episodes can differ even among members of the same family.

Bernard-Soulier syndrome is caused by pathogenic variants in any of three genes—GP1BA, GP1BB, or GP9. These genes provide instructions for building the glycoprotein Ib-IX-V complex on the platelet surface, a critical receptor that anchors platelets to damaged blood vessels. When both copies of one of these genes carry a pathogenic change, the receptor is deficient or absent, and platelets cannot bind efficiently, leading to impaired clot formation. The condition is inherited in an autosomal recessive pattern, meaning an individual must receive one altered copy of the gene from each parent to be affected. Parents who each carry one altered copy are usually healthy but have a 25 percent chance with each pregnancy of having an affected child. This condition is more common when parents share a common ancestor because they are more likely to carry the same rare variant. Carrier testing may be especially helpful for relatives and families with shared ancestry, and genetic counseling is recommended for discussion of family planning options.

Currently, management focuses on supportive care and prevention of bleeding episodes. Individuals are followed by a hematologist, and treatment plans are tailored to the type and severity of bleeding. Platelet transfusions may be required for major surgery or significant hemorrhage, and affected individuals are generally advised to avoid medications that impair platelet function. Long-term management includes regular surveillance of platelet counts and bleeding history, and care is most effective when coordinated by a multidisciplinary team familiar with inherited bleeding disorders. Patients should discuss management strategies and emergency plans with their healthcare team to determine what is appropriate for their specific situation.

Most people with Bernard-Soulier syndrome lead active lives, but they remain at lifelong risk for bleeding, especially after injury or medical procedures. Outcomes depend on many factors, including baseline platelet function, access to specialized hematologic care, and prompt treatment of bleeding events. With growing awareness of the condition and improved transfusion support, serious complications have become less common. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with a hematologist experienced in inherited platelet disorders and to speak with a genetic counselor about future pregnancies and testing options.