Peripheral Blood Morphology as a Clue to 22q11.2 Deletion Syndrome

A female newborn presented with facial dysmorphism and heart malformation consisting of pulmonary atresia with ventricular septal defect and pulmonary blood supply via aortopulmonary collaterals (Figure 1, bottom panels). The syndromic constellation raised suspicion of 22q11.2 deletion syndrome (22q11.2 DS), which was confirmed by molecular testing. Several weeks later, the child was readmitted because of epistaxis. Routine laboratory testing revealed haemoglobin 21.8 g/dL, haematocrit 66% and platelet count 24 × 109/L. Peripheral blood smear examination showed red blood cell anisopoikilocytosis with circulating reticulocytes and erythroblasts, as well as overt platelet macrocytosis (36% with diameter above the 97.5th percentile of healthy controls) (Figure 1, top panels). Immunofluorescence microscopy demonstrated reduced glycoprotein (GP) Ib/IX expression on platelets (Figure 1, top right panel, inset). 22q11.2 DS, the most common chromosomal microdeletion disorder [2], shows variable phenotypic spectrum overlapping DiGeorge syndrome and velocardiofacial syndrome. Typical features include cardiac anomalies, craniofacial dysmorphisms, velopharyngeal insufficiency, hypoparathyroidism, developmental delay, and immunodeficiency [1, 2]. The 22q11.2 region encompasses GP1BB, encoding the GP1bβ subunit of the platelet receptor for von Willebrand factor (GPIb/IX). Affected patients often show increased platelet size, reduced expression of GPIb/IX and/or thrombocytopenia [3]. This case illustrates how detailed evaluation of the peripheral blood smear can provide unique diagnostic clues leading to the consideration of 22q11.2 DS in the appropriate clinical setting. Remarkably, in this patient, blood cell morphology not only suggested the primary genetic diagnosis through platelet abnormalities but also revealed circulating red blood cell progenitors, indicating reactive erythroid hyperplasia. In this context, these haematological findings, in combination with chronic cyanosis (transcutaneous oxygen saturation 75%–80%), should prompt clinicians to suspect an underlying congenital heart defect. J.P. and L.Z. were responsible for clinical data collection. L.S.P., J.L.F. and C.Z. performed morphologic analyses. C.Z. and J.P. wrote the manuscript. All authors critically revised and accepted the final version of the report. Open access funding enabled and organized by Projekt DEAL. The authors have nothing to report. Informed consent was received from all participants. The authors declare no conflicts of interest. Enquiries about data access should be made to the corresponding author.