CHD7 mutations and CHARGE syndrome: the clinical implications of an expanding phenotype
Résumé
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 gene. This review explores the emerging phenotypic spectrum of mutations, with a special focus on the mild end of the spectrum. We evaluated the clinical characteristics in our own cohort of 280 -positive patients and in previously reported patients with mutations and compared these with previously reported patients with CHARGE syndrome but an unknown status. We then further explored the mild end of the phenotypic spectrum of mutations. We discuss that CHARGE syndrome is primarily a clinical diagnosis. In addition, we propose guidelines for 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 mutation, based on our exploration of the phenotypic spectrum and on our experience in a multidisciplinary outpatient clinic for CHARGE syndrome. CHARGE syndrome is an extremely variable clinical syndrome. analysis can be helpful in the diagnostic process, but the phenotype cannot be predicted from the genotype.
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