Abstract
BackgroundOtologic manifestations are one of the most consistent findings of CHARGE syndrome found in more than 90%. Since genetic analysis of the CHD7 gene has rarely been performed in previous reports dealing with ear abnormalities, the genotypic spectrum of CHD7 mutations was analyzed in deaf patients with CHARGE syndrome, and the clinical considerations concerning auditory rehabilitation were investigated.MethodsNine Korean patients with CHARGE syndrome showing profound hearing loss and semicircular canal aplasia were included. All 38 exons of CHD7 were analyzed by direct sequencing. For splice site variations, in silico and exon-trapping analyses were performed to verify the pathogenicity of nucleotide variations. Clinical features and the outcome of auditory rehabilitation were also analyzed.ResultsEight of 9 patients revealed alterations of the CHD7 gene including 3 frameshift, 2 nonsense, 2 splice site, and 1 missense mutations. Five of 9 patients were clinically diagnosed as atypical CHARGE syndrome but demonstrated various mutations of the CHD7 gene. One familial case showed intra-familial variability. Radiologic findings suggesting cochleovestibular nerve deficiency were identified in most of the patients. Of the 8 patients who underwent cochlear implantation, 5 patients demonstrated favorable outcome. Larger diameter of the cochleovestibular nerve on imaging and absence of severe mental retardation were factors related to better outcome after cochlear implantation rather than the type of CHD7 mutations. Auditory brainstem implantation was performed in two patients who did not benefit from cochlear implantation.ConclusionsGenetic analysis of the CHD7 gene should be performed in cases with semicircular canal aplasia even when other typical features of CHARGE syndrome are absent. For auditory rehabilitation in CHARGE syndrome, cochlear implantation should be strongly recommended in selected cases with favorable prognostic factors. Auditory brainstem implantation may be a viable option in patients with CHARGE syndrome who have failed to benefit from cochlear implantation.
Highlights
CHARGE is an acronym describing a set of conditions including ‘‘C’’oloboma of eye, ‘‘H’’eart malformations, ‘‘A’’tresia of choanae, ‘‘R’’etardation in growth and development, ‘‘G’’enital hypoplasia, and ‘‘E’’ar anomalies
The diagnostic criteria proposed by Blake et al [4] in 1998 and those updated by Verloes [5] emphasizing the importance of semicircular canal hypoplasia or aplasia are widely used today for the clinical diagnosis of CHARGE syndrome
Subjects Among the patients who were enrolled in the auditory rehabilitation program at Severance Hospital, nine patients with profound sensorineural hearing loss showing semicircular canal aplasia on the temporal bone computed tomography (CT) were included in this study
Summary
CHARGE is an acronym describing a set of conditions including ‘‘C’’oloboma of eye, ‘‘H’’eart malformations, ‘‘A’’tresia of choanae, ‘‘R’’etardation in growth and development, ‘‘G’’enital hypoplasia, and ‘‘E’’ar anomalies. The combination of these anomalies was first reported by Hall and Hittner [1,2] in 1979 after which the acronym was proposed by Pagon et al [3] in 1981. Since genetic analysis of the CHD7 gene has rarely been performed in previous reports dealing with ear abnormalities, the genotypic spectrum of CHD7 mutations was analyzed in deaf patients with CHARGE syndrome, and the clinical considerations concerning auditory rehabilitation were investigated
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