title: The Immune Phenotype of Patients with CHARGE Syndrome.
abstract: BACKGROUND
  Recurrent sinopulmonary infections are common in children with CHARGE (Coloboma, Heart disease, choanal Atresia, growth/mental Retardation, Genitourinary malformations, Ear abnormalities) syndrome, but no prospective studies on immune function have been conducted.
  
  
  OBJECTIVE
  This study aims to examine and compare the immune phenotype of patients with CHARGE syndrome to those with 22q11.2 deletion and healthy controls.
  
  
  METHODS
  A total of 21 patients attended a multidisciplinary CHARGE clinic. All patients had CHD7 mutational analysis performed. Patients with CHARGE syndrome had lymphocyte subsets, immunoglobulins (IgG, A, M), functional protein, and polysaccharide vaccine responses measured at initial evaluation. A total of 55 healthy controls were prospectively recruited, whereas 40 patients with 22q11.2 deletion were retrospectively identified through medical records. A separate analysis compared serial lymphocyte counts and ionized calcium levels between patients with CHARGE syndrome and those with 22q11.2 deletion in the first 72 months of life.
  
  
  RESULTS
  Despite recurrent childhood ear and chest infections, only 2 children with CHARGE syndrome had an identifiable immune defect (reduced serum IgA). In contrast, T-cell lymphopenia, low immunoglobulin levels, and specific antibody deficiency were noted in patients with 22q11.2 deletion. A greater proportion of patients with 22q11.2 deletion had persistent lymphopenia (57% vs 30%) and hypocalcemia (60% vs 37.5%) compared with patients with CHARGE syndrome in the first 72 months of life.
  
  
  CONCLUSIONS
  Although phenotypic overlap exists between CHARGE and 22q11.2 deletion syndromes, no significant immune defects were detected in this cohort of patients with CHARGE syndrome at the time of testing. Lymphopenia and hypocalcemia occur in both conditions early in life, but is more pronounced in patients with 22q11.2 deletion.
authors.affiliation: Department of Allergy and Immunology, The Children's Hospital at Westmead, Sydney, Australia. Electronic address: peter.hsu@health.nsw.gov.au.
authors.forename: Peter
authors.initials: P
authors.lastname: Hsu
authors.affiliation: Department of Clinical Genetics, The Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Ma
authors.affiliation: Biostatistics, NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Barnes
authors.affiliation: Department of Clinical Genetics, The Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Meredith
authors.initials: M
authors.lastname: Wilson
authors.affiliation: Department of Clinical Genetics, Erasmus MC University Medical Centre, Rotterdam, the Netherlands.
authors.forename: Lies H
authors.initials: LH
authors.lastname: Hoefsloot
authors.affiliation: Department of Human Genetics, Radbound University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Tuula
authors.initials: T
authors.lastname: Rinne
authors.affiliation: Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Craig
authors.initials: C
authors.lastname: Munns
authors.affiliation: Department of Paediatrics, St George Private Hospital, Sydney, Australia.
authors.forename: George
authors.initials: G
authors.lastname: Williams
authors.affiliation: Department of Allergy and Immunology, The Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Melanie
authors.initials: M
authors.lastname: Wong
authors.affiliation: Department of Allergy and Immunology, The Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Sam
authors.initials: S
authors.lastname: Mehr
mesh_terms: D058747:CHARGE Syndrome / Q000175:diagnosis* / Q000276:immunology; D002118:Calcium / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004265:DNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000175:diagnosis* / Q000276:immunology; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D011446:Prospective Studies
chemical_list: D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D004265:DNA Helicases; C491434:CHD7 protein, human; D002118:Calcium
keywords: 22q11.2 deletion syndrome; CHARGE syndrome; Lymphopenia; Specific antibody deficiency