Clinical Phenotype of Bernard Soulier Syndrome Case Resulting from Compound Heterozygous Inheritance
Location
Culp Ballroom
Start Date
4-7-2022 9:00 AM
End Date
4-7-2022 12:00 PM
Poster Number
28
Faculty Sponsor’s Department
Pediatrics
Name of Project's Faculty Sponsor
Myesa Emberesh
Additional Sponsors
Marcela Popescu MD, St Jude Tri-Cities Affiliate Clinic, Johnson City, TN.
Competition Type
Competitive
Type
Poster Case Study Presentation
Project's Category
Blood Diseases
Abstract or Artist's Statement
Background: Bernard Soulier Syndrome (BSS) is a rare, autosomal recessive inheritance disorder of platelet function. Estimated to affect one per one million, there are currently only 200 cases reported worldwide presenting more commonly in families with parental consanguinity.
This syndrome occurs when there is a genetic defect in the subunits (GPIb-alpha, GPIB-beta, and GP9) that form the GPIb-IX-V complex. The result is inadequate binding to von Willebrand factor. The clotting cascade is, therefore, unable to begin, causing symptoms of excessive and prolonged bleeding.
Objectives: We report a case with multiple episodes of exaggerated bleeding and easy bruising.
Methods: We analyzed complete blood count, coagulation studies, platelet aggregation assays, platelet glycoprotein expression by flow cytometry, as well as screened both patient and parents for relevant genes responsible for BSS.
Results: 14-month-old Caucasian male born at 38w3d gestational age, non-consanguineous parents with multiple episodes of exaggerated bleeding and easy bruising from minor injuries. His symptoms started early in life with excessive bleeding after circumcision. No history of intramuscular, joint, or intracranial bleeding.
Complete blood counts showed macrothrombocytopenia (98 X109 /L MPV 12.3 fl) no leukocyte inclusion bodies on peripheral smear. Coagulation tests (prothrombin time, activated partial thromboplastin time, vWF antigen, and vW-Ristocetin cofactor activity, platelet function assay) were normal. Platelet glycoprotein expression by flow cytometry revealed significantly reduced binding of monoclonal antibodies to platelet GPIb and normal GPIIb/IIIa. Comprehensive platelet disorder panel revealed two clinically significant variants missense mutations in the GP9 gene (P.Cys135 Tyr and P.Asn61Ser) These variants were on opposite alleles and results were consistent with the diagnosis of Bernard Soulier syndrome (BSS). The mother reported heavy menstrual cycles, the father had no significant bleeding symptoms, and both parents had normal platelet counts. Target genetic testing identified these two distinct missense mutations from both Mother and Father of the child.
Conclusion: The two rare variants occurring on the gene for GPIX (GP9) increase the number of known genetic defects associated with the manifestation of Bernard Soulier Syndrome.
Clinical Phenotype of Bernard Soulier Syndrome Case Resulting from Compound Heterozygous Inheritance
Culp Ballroom
Background: Bernard Soulier Syndrome (BSS) is a rare, autosomal recessive inheritance disorder of platelet function. Estimated to affect one per one million, there are currently only 200 cases reported worldwide presenting more commonly in families with parental consanguinity.
This syndrome occurs when there is a genetic defect in the subunits (GPIb-alpha, GPIB-beta, and GP9) that form the GPIb-IX-V complex. The result is inadequate binding to von Willebrand factor. The clotting cascade is, therefore, unable to begin, causing symptoms of excessive and prolonged bleeding.
Objectives: We report a case with multiple episodes of exaggerated bleeding and easy bruising.
Methods: We analyzed complete blood count, coagulation studies, platelet aggregation assays, platelet glycoprotein expression by flow cytometry, as well as screened both patient and parents for relevant genes responsible for BSS.
Results: 14-month-old Caucasian male born at 38w3d gestational age, non-consanguineous parents with multiple episodes of exaggerated bleeding and easy bruising from minor injuries. His symptoms started early in life with excessive bleeding after circumcision. No history of intramuscular, joint, or intracranial bleeding.
Complete blood counts showed macrothrombocytopenia (98 X109 /L MPV 12.3 fl) no leukocyte inclusion bodies on peripheral smear. Coagulation tests (prothrombin time, activated partial thromboplastin time, vWF antigen, and vW-Ristocetin cofactor activity, platelet function assay) were normal. Platelet glycoprotein expression by flow cytometry revealed significantly reduced binding of monoclonal antibodies to platelet GPIb and normal GPIIb/IIIa. Comprehensive platelet disorder panel revealed two clinically significant variants missense mutations in the GP9 gene (P.Cys135 Tyr and P.Asn61Ser) These variants were on opposite alleles and results were consistent with the diagnosis of Bernard Soulier syndrome (BSS). The mother reported heavy menstrual cycles, the father had no significant bleeding symptoms, and both parents had normal platelet counts. Target genetic testing identified these two distinct missense mutations from both Mother and Father of the child.
Conclusion: The two rare variants occurring on the gene for GPIX (GP9) increase the number of known genetic defects associated with the manifestation of Bernard Soulier Syndrome.