title: Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome).
abstract: BACKGROUND
  Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a rare autosomal recessive disease characterised by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after PHA stimulation of lymphocytes. Hypomethylation of DNA of a small fraction of the genome is an unusual feature of ICF patients which is explained by mutations in the DNA methyltransferase gene DNMT3B in some, but not all, ICF patients.
  
  
  OBJECTIVE
  To obtain a comprehensive description of the clinical features of this syndrome as well as genotype-phenotype correlations in ICF patients.
  
  
  METHODS
  Data on ICF patients were obtained by literature search and additional information by means of questionnaires to corresponding authors.
  
  
  CONCLUSIONS
  45 patients all with proven centromeric instability were included in this study. Facial dysmorphism was found to be a common characteristic (n = 41/42), especially epicanthic folds, hypertelorism, flat nasal bridge and low set ears. Hypo- or agammaglobulinaemia was demonstrated in nearly all patients (n = 39/44). Opportunistic infections were seen in several patients, pointing to a T cell dysfunction. Haematological malignancy was documented in two patients. Life expectancy of ICF patients is poor, especially those with severe infections in infancy or chronic gastrointestinal problems and failure to thrive. Early diagnosis of ICF is important since early introduction of immunoglobulin supplementation can improve the course of the disease. Allogeneic stem cell transplantation should be considered as a therapeutic option in patients with severe infections or failure to thrive. Only 19 of 34 patients showed mutations in DNMT3B, suggesting genetic heterogeneity. No genotype-phenotype correlation was found between patients with and without DNMT3B mutations.
authors: Department of Pediatric Immunology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors: M M
authors: MM
authors: Hagleitner
authors: A
authors: A
authors: Lankester
authors: P
authors: P
authors: Maraschio
authors: M
authors: M
authors: Hultén
authors: J P
authors: JP
authors: Fryns
authors: C
authors: C
authors: Schuetz
authors: G
authors: G
authors: Gimelli
authors: E G
authors: EG
authors: Davies
authors: A
authors: A
authors: Gennery
authors: B H
authors: BH
authors: Belohradsky
authors: R
authors: R
authors: de Groot
authors: E J A
authors: EJ
authors: Gerritsen
authors: T
authors: T
authors: Mattina
authors: P J
authors: PJ
authors: Howard
authors: A
authors: A
authors: Fasth
authors: I
authors: I
authors: Reisli
authors: D
authors: D
authors: Furthner
authors: M A
authors: MA
authors: Slatter
authors: A J
authors: AJ
authors: Cant
authors: G
authors: G
authors: Cazzola
authors: P J
authors: PJ
authors: van Dijken
authors: M
authors: M
authors: van Deuren
authors: J C
authors: JC
authors: de Greef
authors: S M
authors: SM
authors: van der Maarel
authors: C M R
authors: CM
authors: Weemaes
mesh_terms: D000293:Adolescent; D000328:Adult; D002503:Centromere / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D043171:Chromosomal Instability; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000473:pathology; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype; D013577:Syndrome; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D000097584:DNA Methyltransferase 3B