CHD7 mutations and CHARGE syndrome: the clinical implications of an expanding phenotype
JEH Bergman, N Janssen, LH Hoefsloot… - Journal of medical …, 2011 - jmg.bmj.com
JEH Bergman, N Janssen, LH Hoefsloot, MCJ Jongmans, RMW Hofstra…
Journal of medical genetics, 2011•jmg.bmj.comBackground 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 c oloboma, congenital h
eart defects, choanal a tresia, r etardation of growth and development, g enital hypoplasia,
and e ar anomalies associated with deafness. This typical combination of clinical features is
caused by autosomal dominant mutations in the CHD7 gene. Objective To explore the …
syndrome, of which the complete phenotypic spectrum was only revealed after identification
of the causative gene in 2004. CHARGE is an acronym for ocular c oloboma, congenital h
eart defects, choanal a tresia, r etardation of growth and development, g enital hypoplasia,
and e ar anomalies associated with deafness. This typical combination of clinical features is
caused by autosomal dominant mutations in the CHD7 gene. Objective To explore the …
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.
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