title: Immune Dysfunction in Children with CHARGE Syndrome: A Cross-Sectional Study.
abstract: CHARGE syndrome is a variable, multiple congenital malformation syndrome. Patients with CHARGE syndrome have frequent infections that are presumed to be due to anatomical anomalies of the craniofacial region and upper airway, and cranial nerve problems resulting in swallowing difficulties and aspiration. The possible contribution of immunological abnormalities to these infections has not been systematically studied even though immune deficiencies have been described in patients with 22q11.2 deletion syndrome, a condition which shares remarkable clinical overlap with CHARGE syndrome. We assessed the frequency and nature of immune dysfunction in 24 children with genetically proven CHARGE syndrome. All patients, or their parents, completed a questionnaire on infectious history. Their immune system was extensively assessed through full blood counts, immunoglobulin levels, lymphocyte subpopulations, peripheral B- and T-cell differentiation, T-receptor excision circle (TREC) analysis, T-cell function, and vaccination responses. All CHARGE patients had a history of infections (often frequent), mainly otitis media and pneumonia, leading to frequent use of antibiotics and to hospital admissions. Decreased T-cell numbers were found in 12 (50%) patients, presumably caused by insufficient thymic output since TREC amounts were also diminished in CHARGE patients. Despite normal peripheral B-cell differentiation and immunoglobulin production in all patients, 83% of patients had insufficient antibody titers to one or more early childhood vaccinations. Based on our results, we recommend immunological evaluation of CHARGE patients with recurrent infections.
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Monica T Y
authors.initials: MT
authors.lastname: Wong
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Laboratory Medicine, Medical Immunology, Groningen, The Netherlands.
authors.forename: Annechien J A
authors.initials: AJ
authors.lastname: Lambeck
authors.affiliation: Erasmus MC, University Medical Centre Rotterdam, Department of Immunology, Rotterdam, The Netherlands.
authors.forename: Mirjam
authors.initials: M
authors.lastname: van der Burg
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Epidemiology, Groningen, The Netherlands.
authors.forename: Sacha
authors.initials: S
authors.lastname: la Bastide-van Gemert
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Laboratory Medicine, Medical Immunology, Groningen, The Netherlands.
authors.forename: Lianne A
authors.initials: LA
authors.lastname: Hogendorf
authors.affiliation: University of Groningen, University Medical Centre Groningen, Department of Genetics, Groningen, The Netherlands.
authors.forename: Conny M A
authors.initials: CM
authors.lastname: van Ravenswaaij-Arts
authors.affiliation: University of Groningen, University Medical Centre Groningen, Beatrix Children's Hospital, Department of Paediatrics, Infectious Diseases and Immunology section, Groningen, The Netherlands.
authors.forename: Elisabeth H
authors.initials: EH
authors.lastname: Schölvinck
mesh_terms: D000293:Adolescent; D001772:Blood Cell Count; D058747:CHARGE Syndrome / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007223:Infant; D008297:Male; D014611:Vaccination