A rare pair in one patient - Bernard-Soulier syndrome unraveled by 22q11.2 microdeletion syndrome

Introduction: The 22q11.2 deletion syndrome is one of the
most common microdeletion syndromes. Bernard-Soulier
syndrome, in turn, is a rare autosomal recessive bleeding
disorder (prevalence <1:1 000 000) with dysfunctional
glycoprotein Ib-V-IX complex, responsible for the adhesion
activity of platelets. We report a patient having both
diseases.
Case report: A boy who was admitted to hospital on the
third day of life due to epistaxis, petechias and umbilical
cord bleeding. Brain MRI showed subdural hematoma
among cerebellar lobes. Blood count revealed severe
thrombocytopenia (8 x 103
/uL), that required several
platelet infusions and did not improve with immunoglobulin
treatment. An NGS analysis for Bleeding disorder gene
panel was ordered, with CNV analysis. On the second
month of life flow cytometry revealed reduced CD42b
expressivity.
Results: The NGS gene panel results revealed a
heterozygous pathogenic 22q11.2 microdeletion, encompassing 73 genes with GP1BB gene included. The analysis
also showed a heterozygous likely pathogenic variant in
GP1BB gene c.395T>A, p.(Leu132Gln). The combination
of the microdeletion on one and the mutation on the other
GP1BB allele explains the bleeding disorder of our patient
and confirms in him Bernard-Soulier syndrome. 22q11.2
microdeletion syndrome was not suspected before the DNA
analysis. Afterwards at a repeated consultation the patient
demonstrated signs of velopharyngeal insufficiency but as
yet no other signs of the Velocardiofacial syndrome.
Conclusions: In patients with early onset bleeding
disorder genetic testing with CNV analysis must be
performed in order to not miss an autosomal recessive
disease unmasked by a seemingly presymptomatic frequent
microdeletion syndrome