title: The 11q Terminal Deletion Disorder Jacobsen Syndrome is a Syndromic Primary Immunodeficiency.
abstract: BACKGROUND
  Jacobsen syndrome (JS) is a rare contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. Clinical features include physical and mental growth retardation, facial dysmorphism, thrombocytopenia, impaired platelet function and pancytopenia. In case reports, recurrent infections and impaired immune cell function compatible with immunodeficiency were described. However, Jacobsen syndrome has not been recognized as an established syndromic primary immunodeficiency.
  
  
  OBJECTIVE
  To evaluate the presence of immunodeficiency in a series of 6 patients with JS.
  
  
  METHODS
  Medical history of 6 patients with JS was evaluated for recurrent infections. IgG, IgA, IgM and specific antibodies against S. pneumoniae were measured. Response to immunization with a polysaccharide vaccine (Pneumovax) was measured and B and T lymphocyte subset analyses were performed using flowcytometry.
  
  
  RESULTS
  Five out of 6 patients suffered from recurrent infections. These patients had low IgG levels and impaired response to S. pneumoniae polysaccharide vaccination. Moreover, we also found a significant decrease in the absolute number of memory B cells, suggesting a defective germinal center function. In a number of patients, low numbers of T lymphocytes and NK cells were found.
  
  
  CONCLUSIONS
  Most patients with JS suffer from combined immunodeficiency in the presence of recurrent infections. Therefore, we consider JS a syndromic primary immunodeficiency. Early detection of immunodeficiency may reduce the frequency and severity of infections. All JS patients should therefore undergo immunological evaluation. Future studies in a larger cohort of patients will more precisely define the pathophysiology of the immunodeficiency in JS.
authors.affiliation: Department of Internal Medicine, Erasmus MC, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. v.dalm@erasmusmc.nl.|Department of Immunology, Erasmus MC, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. v.dalm@erasmusmc.nl.
authors.forename: Virgil A S H
authors.initials: VA
authors.lastname: Dalm
authors.affiliation: Department of Immunology, Erasmus MC, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.|Department of Pediatric Infectious disease and Immunology, Erasmus MC, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Gertjan J A
authors.initials: GJ
authors.lastname: Driessen
authors.affiliation: Department of Immunology, Erasmus MC, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Barbara H
authors.initials: BH
authors.lastname: Barendregt
authors.affiliation: Department of Internal Medicine, Erasmus MC, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.|Department of Immunology, Erasmus MC, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Petrus M
authors.initials: PM
authors.lastname: van Hagen
authors.affiliation: Department of Immunology, Erasmus MC, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
authors.forename: Mirjam
authors.initials: M
authors.lastname: van der Burg
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D002648:Child; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D003718:Denmark; D005260:Female; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000453:epidemiology* / Q000276:immunology; D007239:Infections / Q000453:epidemiology* / Q000276:immunology; D054868:Jacobsen Distal 11q Deletion Syndrome / Q000453:epidemiology* / Q000276:immunology; D008297:Male; D055815:Young Adult
keywords: 11q terminal deletion disorder; Immunodeficiency; Jacobsen syndrome; humoral; infections