RESUMO
We present the case of a Dutch family with a new mutation (c523_528dup) in GATA3 causing HDR syndrome. HDR syndrome is characterised by hypoparathyroidism, deafness and renal defects. In this study, we describe the audiometric characteristics of 5 patients from this family. Their hearing impairment was congenital, bilateral and symmetric. Audiograms showed mild-to-moderate hearing impairment with a flat audiogram configuration. Higher frequencies tended to be affected more strongly. Cross-sectional analyses showed no progression, and a mean audiogram was established. Psychophysical measurements in 3 HDR patients - including speech reception in noise, loudness scaling, gap detection and difference limen for frequency - were obtained to assess hearing function in greater detail. Overall, the results of the psychophysical measurements indicated characteristics of outer hair cell loss. CT scanning showed no anomalies in 3 of the HDR patients. Although 2 patients displayed vestibular symptoms, no anomalies in the vestibular system were found by vestibulo-ocular examination. Our results are in agreement with the theory that outer hair cell malfunctioning can play a major role in HDR syndrome.
Assuntos
Fator de Transcrição GATA3/genética , Perda Auditiva Neurossensorial/genética , Hipoparatireoidismo/genética , Mutação , Nefrose/genética , Audiometria de Tons Puros , Feminino , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Hipoparatireoidismo/fisiopatologia , Masculino , Nefrose/fisiopatologia , Países Baixos , Linhagem , Fenótipo , Percepção da Fala/fisiologia , Síndrome , Testes de Função VestibularRESUMO
Since deafness is the most common sensorineural disorder in humans, better understanding of the underlying causes is necessary to improve counseling and rehabilitation. A Dutch family with autosomal dominantly inherited sensorineural hearing loss was clinically and genetically assessed. The MYO6 gene was selected to be sequenced because of similarities with other, previously described DFNA22 phenotypes and a pathogenic c.3610C > T (p.R1204W) mutation was found to co-segregate with the disease. This missense mutation results in a flat configured audiogram with a mild hearing loss, which becomes severe to profound and gently to steeply downsloping later in life. The age-related typical audiograms (ARTA) constructed for this family resemble presbyacusis. Speech audiometry and results of loudness scaling support the hypothesis that the phenotype of this specific MYO6 mutation mimics presbyacusis.
Assuntos
Perda Auditiva Neurossensorial/genética , Audição/genética , Mutação de Sentido Incorreto , Cadeias Pesadas de Miosina/genética , Presbiacusia/genética , Estimulação Acústica , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Audiometria de Tons Puros , Audiometria da Fala , Limiar Auditivo , Criança , Análise Mutacional de DNA , Progressão da Doença , Feminino , Predisposição Genética para Doença , Perda Auditiva Neurossensorial/fisiopatologia , Perda Auditiva Neurossensorial/psicologia , Hereditariedade , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Presbiacusia/fisiopatologia , Presbiacusia/psicologia , Percepção da Fala , Vestíbulo do Labirinto/fisiopatologia , Adulto JovemRESUMO
OBJECTIVE: To evaluate hearing impairment and cochlear function in non-ocular Stickler syndrome. STUDY DESIGN: Multifamily study. PATIENTS & METHODS: Ten patients from two different families with non-ocular Stickler syndrome (Stickler syndrome type 3) were included. Six members of the first family and four members of the second family participated in this study. Otorhinolaryngologic examinations were performed. Pure-tone and speech audiograms were obtained. Longitudinal analysis was performed. Psychophysical measurements, including loudness scaling, gap detection, difference limen for frequency and speech perception in noise were administered to assess cochlear function at a deeper level. RESULTS: Affected individuals in the first family were carriers of a heterozygous splice donor mutation in the COL11A2 gene. Affected individuals in the second family were carriers of a novel heterozygous missense mutation in COL11A2. Both families showed bilateral, non-progressive hearing impairment with childhood onset. The severity of the hearing impairment exhibited inter- and intrafamilial variability and was mostly mild to moderate. The results of the psychophysical measurements were similar to those previously published for DFNA8/12 (TECTA) and DFNA13 (COL11A2) patients and thus consistent with an intra-cochlear conductive hearing impairment. This is in line with the theory that mutations in COL11A2 affect tectorial membrane function. CONCLUSION: Hearing impairment in non-ocular Stickler syndrome is characterized by non-progressive hearing loss, present since childhood, and mostly mild to moderate in severity. Psychophysical measurements in non-ocular Stickler patients were suggestive of intra-cochlear conductive hearing impairment.