Bernard Soulier Syndrome: A Rare Bleeding Disorder with a Wide Range of Genetic Defects

General information on the syndrome

Bernard Soulier Syndrome (BSS) was described more than 60 years ago as a severe, and potentially fatal, congenital bleeding disorder. The first case was reported in 1948 by Jean Bernard and Jean-Pierre Soulier on a young male patient with a prolonged bleeding time, low platelet counts, and extremely large platelets. They termed the disorder “congenital hemorrhagiparous thrombocytic dystrophy” [1]. Since then, some individuals have been described with a similar disorder. Based on data reported concerning European, North American, and Japanese populations, the frequency of homozygous BSS has been estimated to be approximately one in one million [2] and, according to the Hardy-Weinberg Law, the frequency of heterozygotes is 1 in 500 [3].

Abstract

Bernard Soulier Syndrome (BSS) is a rare inherited bleeding disorder caused by a quantitative or qualitative defect in glycoprotein (GP)Ib-IX-V complex, the receptor for the von Willebrand factor (vWF). This complex plays a major role in platelet adhesion at sites of vascular injury through binding to vWF. It is also involved in the thrombin induced platelet activation. BSS is usually inherited in an autosomal recessive manner and is characterized by a prolonged bleeding time, thrombocytopenia, and giant platelets. Clinical manifestations include a series of purpura, epistaxis, menorrhagia, gingival, and gastric bleeding. Diagnosis is based on prolonged skin bleeding time, macrothrombocytopenia, defective ristocetin-induced platelet aggregation, and the exploration of GPIb-IX-V complex expression. The complex is composed of four subunits: GPIbα, GPIbβ, GPIX, and GPV, but the principal candidate genes for this disease are GPIbα, GPIbβ, and GPIX. These genes are unique in the genome and share the scarcity of introns with one or two introns per gene. In this review, we give an overview of the mutations occurring in the candidate genes with an emphasis on compound heterozygous mutations as well as on founder mutations.

Keywords

Bernard Soulier syndrome, bleeding disorder, GPIb-IX-V complex, thrombocytopenia, giant platelets, founder mutation, compound heterozygous