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CHD7 mutations and CHARGE syndrome: the clinical implications of an expanding phenotype
  1. J E H Bergman1,
  2. N Janssen1,
  3. L H Hoefsloot2,
  4. M C J Jongmans2,
  5. R M W Hofstra1,
  6. C M A van Ravenswaaij-Arts1
  1. 1Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
  2. 2Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
  1. Correspondence to Dr C M A van Ravenswaaij-Arts, Department of Genetics, University Medical Centre Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands; c.m.a.van.ravenswaaij{at}


Background CHARGE syndrome is a highly variable, multiple congenital anomaly syndrome, of which the complete phenotypic spectrum was only revealed after identification of the causative gene in 2004. CHARGE is an acronym for ocular coloboma, congenital heart defects, choanal atresia, retardation of growth and development, genital hypoplasia, and ear anomalies associated with deafness. This typical combination of clinical features is caused by autosomal dominant mutations in the CHD7 gene.

Objective To explore the emerging phenotypic spectrum of CHD7 mutations, with a special focus on the mild end of the spectrum.

Methods We evaluated the clinical characteristics in our own cohort of 280 CHD7 positive patients and in previously reported patients with CHD7 mutations and compared these with previously reported patients with CHARGE syndrome but an unknown CHD7 status. We then further explored the mild end of the phenotypic spectrum of CHD7 mutations.

Results We discuss that CHARGE syndrome is primarily a clinical diagnosis. In addition, we propose guidelines for CHD7 analysis and indicate when evaluation of the semicircular canals is helpful in the diagnostic process. Finally, we give updated recommendations for clinical surveillance of patients with a CHD7 mutation, based on our exploration of the phenotypic spectrum and on our experience in a multidisciplinary outpatient clinic for CHARGE syndrome.

Conclusion CHARGE syndrome is an extremely variable clinical syndrome. CHD7 analysis can be helpful in the diagnostic process, but the phenotype cannot be predicted from the genotype.

  • CHARGE syndrome
  • CHD7
  • phenotypic spectrum
  • clinical genetics
  • genetic screening/counselling
  • molecular genetics

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  • Funding Netherlands Organisation for Health Research and Fund NutsOhra.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Ethics committee approval not necessary. Clinical information was collected with informed consent and subsequently used strictly anonymously according to local ethical regulations, except for some individual patients who might be identifiable in the paper, but who all gave their consent.

  • Provenance and peer review Not commissioned; externally peer reviewed.