Subject(s)
Abnormalities, Multiple/genetics , Forkhead Transcription Factors/genetics , Intestinal Diseases/genetics , Mutation, Missense , Polyendocrinopathies, Autoimmune/genetics , T-Lymphocytes, Regulatory , Abnormalities, Multiple/immunology , Autoimmune Diseases/genetics , Fatal Outcome , Forkhead Transcription Factors/metabolism , Gene Expression Regulation , Humans , Infant, Newborn , Infant, Premature , Intestinal Diseases/immunology , Male , Phenotype , Polyendocrinopathies, Autoimmune/immunology , SyndromeABSTRACT
OBJECTIVE: The objective of this study was to characterize the temporal bone phenotype associated with a mutation of GJB2 (encoding connexin 26). STUDY DESIGN: The authors conducted correlative clinical, molecular genetic, and postmortem histopathologic analysis. METHODS: The study subject was a male infant with keratitis-ichthyosis-deafness (KID) syndrome. We performed a nucleotide sequence analysis of GJB2 and a histopathologic analysis of the temporal bones. RESULTS: The subject was heterozygous for G45E, a previously reported KID syndrome mutation of GJB2. The primary inner ear abnormality was dysplasia of the cochlear and saccular neuroepithelium. CONCLUSIONS: GJB2 mutations can cause deafness in KID syndrome, and possibly in other GJB2 mutant phenotypes, by disrupting cochlear differentiation.
Subject(s)
Cochlea/abnormalities , Connexins/genetics , Deafness/genetics , Ichthyosis/genetics , Keratitis/genetics , Saccule and Utricle/abnormalities , Connexin 26 , Hearing Loss, Sensorineural/genetics , Heterozygote , Humans , Ichthyosis/complications , Infant, Newborn , Keratitis/complications , Male , Mutation , Syndrome , Temporal Bone/abnormalities , Temporal Bone/pathologyABSTRACT
We report two siblings with a family history of Waardenburg's syndrome (WS) for whom the audiological profile corresponds to auditory neuropathy (AN). They have; (1) bilateral severe to profound hearing loss, (2) robust oto-acoustic emissions (OAEs) in both ears, and (3) no auditory evoked responses at 95 dBnHL bilaterally. Electrocochleography (ECochG) and auditory middle and late latency potentials were performed in one of the children. Results showed cochlear and neural activities in both ears. Central auditory responses were not conclusive. These children did not have any history of neonatal illness and one child was diagnosed with AN at the age of 3 weeks and the other at the age of 11 months.
Subject(s)
Hearing Loss, Bilateral/genetics , Otoacoustic Emissions, Spontaneous/physiology , Peripheral Nervous System Diseases/genetics , Siblings , Waardenburg Syndrome/genetics , Child , Child, Preschool , Evoked Potentials, Auditory, Brain Stem/physiology , Female , Hearing Loss, Bilateral/physiopathology , Humans , Male , Peripheral Nervous System Diseases/physiopathology , Waardenburg Syndrome/physiopathologyABSTRACT
OBJECTIVE: Evaluation of the auditory manifestations of Keratitis-Ichthyosis-Deafness (KID) syndrome, a rare genodermatosis characterized by follicular hyperkeratosis, vascularizing keratitis, and congenital hearing loss. STUDY DESIGN: Five individuals with sporadic KID syndrome were evaluated in the outpatient audiology clinic at the Warren Grant Magnuson Clinical Center of the National Institutes of Health. METHODS: Audiologic examinations included pure-tone audiometry, speech audiometry, and middle ear immittance testing. Auditory brainstem responses and otoacoustic emissions were analyzed in 2 subjects. RESULTS: Four subjects had prelingual, bilateral, profound sensorineural hearing loss, whereas the fifth subject had significant residual hearing that exhibited no progression on serial audiograms. All 5 subjects had a history of non-erosive keratosis obturans and cutaneous cysts in the external ear canals that prevented continuous use of ear molds. CONCLUSIONS: The sensorineural hearing loss in KID syndrome is generally prelingual and profound. This combination of auditory and cutaneous phenotypes is similar to those previously reported for KID syndrome. KID syndrome presents a difficult challenge for communication rehabilitation because keratitis may impair the perception of sign and spoken language, and the cutaneous manifestations routinely curtail use of external amplification devices.
