RESUMEN
Hematopoietic cell transplantation (HCT) is a curative treatment option for both malignant and nonmalignant diseases. Success of the procedure mainly depends on disease control and treatment-related complications. Pharmacotherapy plays a major role in HCT and significantly impacts the outcomes. Main drug use within HCT includes conditioning, GvHD prophylaxis, and prevention/treatment of infections.Increasing evidence suggests individualized dosing in (pediatric) HCT may improve outcome. Dose individualization may result in a better predictable drug treatment in terms of safety and efficacy, including timely immune reconstitution after HCT and optimal tumor or disease control, which may result in improved survival chances.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Niño , Humanos , Acondicionamiento PretrasplanteRESUMEN
This study focuses on further characterization of the audiovestibular phenotype and on genotype-phenotype correlations of DFNB77, an autosomal recessive type of hearing impairment (HI). DFNB77 is associated with disease-causing variants in LOXHD1, and is genetically and phenotypically highly heterogeneous. Heterozygous deleterious missense variants in LOXHD1 have been associated with late-onset Fuchs corneal dystrophy (FCD). However, up to now screening for FCD of heterozygous carriers in DFNB77 families has not been reported. This study describes the genotype and audiovestibular phenotype of 9 families with DFNB77. In addition, carriers within the families were screened for FCD. Fifteen pathogenic missense and truncating variants were identified, of which 12 were novel. The hearing phenotype showed high inter- and intrafamilial variation in severity and progression. There was no evidence for involvement of the vestibular system. None of the carriers showed (pre-clinical) symptoms of FCD. Our findings expand the genotypic and phenotypic spectrum of DFNB77, but a clear correlation between the type or location of the variant and the severity or progression of HI could not be established. We hypothesize that environmental factors or genetic modifiers are responsible for phenotypic differences. No association was found between heterozygous LOXHD1 variants and the occurrence of FCD in carriers.
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Proteínas Portadoras/genética , Distrofia Endotelial de Fuchs/genética , Predisposición Genética a la Enfermedad , Pérdida Auditiva Sensorineural/genética , Adolescente , Adulto , Audiometría , Niño , Preescolar , Femenino , Distrofia Endotelial de Fuchs/fisiopatología , Estudios de Asociación Genética , Genotipo , Pérdida Auditiva Sensorineural/fisiopatología , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Mutación Missense , Linaje , FenotipoRESUMEN
OBJECTIVE: Genetic testing for hereditary hearing impairment has become more routinely available as a diagnostic tool in the outpatient clinic. However, little is known about the psychological impact of a genetic diagnosis. To evaluate this impact, an exploratory study was conducted. DESIGN: Prospectively, 48 individuals who underwent genetic testing for hereditary hearing impairment were included in this study. Study participants were asked to fill out the following questionnaires: Hospital Anxiety Depression Scale, Impact of Event Scale, Self-Efficacy 24, Illness Cognition Questionnaire and the Inventory for Social Reliance. Questionnaires were filled out on three occasions: before genetic testing, directly after counselling on either positive or negative test results, and six weeks thereafter. RESULTS: No significant differences were found between the group that received a genetic diagnosis for their hearing impairment and the group that did not. CONCLUSION: This study did not demonstrate differences between receiving a genetic diagnosis or not; however, special attention to psychological well-being should be offered to hearing-impaired patients who seek a genetic diagnosis for their hearing impairment. Additionally, the psychological impact of sensorineural hearing impairment might be greater than the impact of a genetic diagnosis itself. Based on the current exploratory study, there are no psychological reasons in favour of or against genetic testing for hereditary hearing impairment.
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Ansiedad/psicología , Depresión/psicología , Pruebas Genéticas/ética , Pérdida Auditiva/diagnóstico , Adulto , Anciano , Ansiedad/epidemiología , Ansiedad/etiología , Depresión/epidemiología , Depresión/etiología , Femenino , Estudios de Seguimiento , Pérdida Auditiva/genética , Pérdida Auditiva/psicología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
To provide an overview of anomalies of the temporal bone in CHARGE syndrome relevant to cochlear implantation (CI), anatomical structures of the temporal bone and the respective genotypes were analysed. In this retrospective study, 42 CTs of the temporal bone of 42 patients with CHARGE syndrome were reviewed in consensus by two head-and-neck radiologists and two otological surgeons. Anatomical structures of the temporal bone were evaluated and correlated with genetic data. Abnormalities that might affect CI surgery were seen, such as a vascular structure, a petrosquamosal sinus (13 %), an underdeveloped mastoid (8 %) and an aberrant course of the facial nerve crossing the round window (9 %) and/or the promontory (18 %). The appearance of the inner ear varied widely: in 77 % of patients all semicircular canals were absent and the cochlea varied from normal to hypoplastic. A stenotic cochlear aperture was observed in 37 %. The middle ear was often affected with a stenotic round (14 %) or oval window (71 %). More anomalies were observed in patients with truncating mutations than with non-truncating mutations. Temporal bone findings in CHARGE syndrome vary widely. Vascular variants, aberrant route of the facial nerve, an underdeveloped mastoid, aplasia of the semicircular canals, and stenotic round window may complicate cochlear implantation.
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Síndrome CHARGE/diagnóstico por imagen , Implantación Coclear , ADN Helicasas/genética , Proteínas de Unión al ADN/genética , Hueso Temporal/anomalías , Adolescente , Adulto , Síndrome CHARGE/complicaciones , Niño , Preescolar , Cóclea/anomalías , Cóclea/diagnóstico por imagen , Implantación Coclear/métodos , Implantes Cocleares , Oído Medio/anomalías , Oído Medio/diagnóstico por imagen , Nervio Facial/anomalías , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Apófisis Mastoides/anomalías , Apófisis Mastoides/diagnóstico por imagen , Persona de Mediana Edad , Otolaringología , Radiología , Estudios Retrospectivos , Ventana Redonda/anomalías , Ventana Redonda/diagnóstico por imagen , Canales Semicirculares/anomalías , Hueso Temporal/diagnóstico por imagen , Hueso Temporal/patología , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To evaluate the benefit of cochlear implantation in patients with Pendred syndrome. DESIGN: Retrospective study. SETTING: Tertiary centre. PARTICIPANTS AND MAIN OUTCOME MEASURES: Speech perception was measured using a phonetically balanced word list at a sound pressure level of 65 dB. Post-operative phoneme scores at 12-month for adults and 36-month for children with Pendred syndrome were compared to scores of patients with an enlarged vestibular aqueduct (EVA) and a reference group with an unknown cause of hearing impairment. Quality of life was measured with the Nijmegen Cochlear Implant Questionnaire to evaluate the differences between pre- and post-implantation. RESULTS: The mean post-operative phoneme scores were as follows: in the Pendred group, 91% (n = 16; SD = 10) for children and 78% (n = 7; SD = 14) for adults; in the reference group, 79% (n = 59; SD = 20) for children and 73% (n = 193; SD = 18) for adults; and in the EVA group, 84% (n = 6; SD = 7) for children and 66% (n = 12; SD = 22) for adults. A significant difference in speech perception was found between the children of the Pendred group and the reference group of 11.4% (SE = 5.2; P = 0.031). Between the adults, a difference of 11.2% (SE = 6.7; P = 0.094) was found. The difference between the Pendred group and the EVA group was 5.7%(SE = 4.5; P = 0.22) for children and 9.9% (SE = 8.7; P = 0.28) for adults. A significant improvement post-implantation in four of the six subdomains of the quality of life questionnaire was found: basic sound perception (P = 0.002), advanced sound perception (P = 0.004), speech production (P = 0.018) and activity limitations (P = 0.018). The two not significant subdomains were self-esteem (P = 0.164) and social interaction (P = 0.107). CONCLUSIONS: After cochlear implantation, children with Pendred syndrome performed better than the reference group with respect to speech perception, however, adults performed similar. No significant differences were found between the Pendred and EVA group. Consequently, during pre-operative counselling, the two groups of patients may be considered comparable in terms of expected speech perception performance after cochlear implantation.
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Implantación Coclear , Bocio Nodular/cirugía , Pérdida Auditiva Sensorineural/cirugía , Niño , Femenino , Humanos , Masculino , Calidad de Vida , Estudios Retrospectivos , Percepción del Habla , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
The installation of deep drains is an engineering approach to remediate land salinised by the influence of shallow groundwater. It is a costly treatment and its economic viability is, in part, dependent on the lateral extent to which the drain increases biological productivity by lowering water tables and soil salinity (referred to as the drains' zone of benefit). Such zones may be determined by assessing the biological productivity response of adjacent vegetation over time. We tested a multi-temporal satellite remote sensing method to analyse temporal and spatial changes in vegetation condition surrounding deep drainage sites at five locations in the Western Australian wheatbelt affected by dryland salinity-Morawa, Pithara, Beacon, Narembeen and Dumbleyung. Vegetation condition as a surrogate for biological productivity was assessed by Normalised Difference Vegetation Index (NDVI) during the peak growing season. Analysis was at the site scale within a 1000 m buffer zone from the drains. There was clear evidence of NDVI increasing with elevation, slope and distance from the drain. After accounting for elevation, slope and distance from the drain, there was a significant increase in NDVI across the five locations after installation of deep drains. Changes in NDVI after drainage were broadly consistent with measured changes at each site in groundwater levels after installation of the deep drains. However, this study assessed the lateral extent of benefit for biological productivity and gave a measure of the area of benefit along the entire length of the drain. The method demonstrated the utility of spring NDVI images for rapid and relatively simple assessment of the change in site condition after implementation of drainage, but approaches for further improvement of the procedure were identified.
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Monitoreo del Ambiente/métodos , Agua Subterránea , Abastecimiento de Agua , Australia , Restauración y Remediación Ambiental , Humanos , Tecnología de Sensores Remotos , Salinidad , Estaciones del AñoRESUMEN
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.
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Factor de Transcripción GATA3/genética , Pérdida Auditiva Sensorineural/genética , Hipoparatiroidismo/genética , Mutación , Nefrosis/genética , Audiometría de Tonos Puros , Femenino , Pérdida Auditiva Sensorineural/fisiopatología , Humanos , Hipoparatiroidismo/fisiopatología , Masculino , Nefrosis/fisiopatología , Países Bajos , Linaje , Fenotipo , Percepción del Habla/fisiología , Síndrome , Pruebas de Función VestibularRESUMEN
Anti-thymocyte globulin (ATG), a polyclonal antibody, is used in allogeneic hematopoietic cell transplantation (HCT) to prevent graft-vs.-host-disease (GvHD) and graft failure (GF). Overexposure to ATG leads to poor early T-cell recovery, which is associated with viral infections and poor survival. Patients with severe inflammation are at high risk for GF and GvHD, and may have active infections warranting swift T-cell recovery. As ATG exposure may be critical in these patients, individualized dosing combined with therapeutic drug monitoring (TDM) may improve outcomes. We describe the individualized dosing approach, an optimal sampling scheme, the assay to measure the active fraction of ATG, and the workflow to perform TDM. Using a previously published population pharmacokinetic (PK) model, we determine the dose to reach optimal exposures associated with low GvHD and rejection, and at the same time promote T-cell recovery. Based on an optimal sampling scheme, peak and trough samples are taken during the first 3 days of once-daily dosing. The fraction of ATG able to bind to T-cells (active ATG) is analyzed using a bio-assay in which Jurkat cells are co-cultured with patient's plasma and the binding is quantified using flow cytometry. TDM is performed based on these ATG concentrations on the third day of dosing; subsequent doses can be adjusted based on the expected area under the curve. We show that individualized ATG dosing with TDM is feasible. This approach is unique in the setting of antibody treatment and may result in better immune reconstitution post-HCT and subsequently better survival chances.
RESUMEN
BACKGROUND: CHARGE syndrome is a non-random clustering of congenital anomalies including coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, ear anomalies, and deafness. A consistent feature in CHARGE syndrome is semicircular canal hypoplasia resulting in vestibular areflexia. Other commonly associated congenital anomalies are facial nerve palsy, cleft lip/palate, and tracheo-oesophageal fistula. Specific behavioural problems, including autistic-like behaviour, have been described. The CHD7 gene on chromosome 8q12.1 was recently discovered as a major gene involved in the aetiology of this syndrome. METHODS: The coding regions of CHD7 were screened for mutations in 107 index patients with clinical features suggestive of CHARGE syndrome. Clinical data of the mutation positive patients were sampled to study the phenotypic spectrum of mutations in the CHD7 gene. RESULTS: Mutations were identified in 69 patients. Here we describe the clinical features of 47 of these patients, including two sib pairs. Most mutations were unique and were scattered throughout the gene. All patients but one fulfilled the current diagnostic criteria for CHARGE syndrome. No genotype-phenotype correlations were apparent in this cohort, which is best demonstrated by the differences in clinical presentation in sib pairs with identical mutations. Somatic mosaicism was detected in the unaffected mother of a sib pair, supporting the existence of germline mosaicism. CONCLUSIONS: CHD7 mutations account for the majority of the cases with CHARGE syndrome, with a broad clinical variability and without an obvious genotype-phenotype correlation. In one case evidence for germline mosaicism was provided.
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Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , ADN Helicasas/genética , Proteínas de Unión al ADN/genética , Mutación , Adolescente , Adulto , Enfermedades del Sistema Nervioso Central/diagnóstico , Enfermedades del Sistema Nervioso Central/genética , Niño , Preescolar , Atresia de las Coanas/diagnóstico , Atresia de las Coanas/genética , Coloboma/diagnóstico , Coloboma/genética , Análisis Mutacional de ADN , Femenino , Pruebas Genéticas , Edad Gestacional , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/genética , Humanos , Lactante , Recién Nacido , Masculino , Enfermedades de la Boca/diagnóstico , Enfermedades de la Boca/genética , Fenotipo , Enfermedades de la Columna Vertebral/diagnóstico , Enfermedades de la Columna Vertebral/genética , Síndrome , Enfermedades Vestibulares/diagnóstico , Enfermedades Vestibulares/genéticaRESUMEN
Common variants in interferon regulatory factor 6 ( IRF6) have been associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) as well as with tooth agenesis (TA). These variants contribute a small risk towards the 2 congenital conditions and explain only a small percentage of heritability. On the other hand, many IRF6 mutations are known to be a monogenic cause of disease for syndromic orofacial clefting (OFC). We hypothesize that IRF6 mutations in some rare instances could also cause nonsyndromic OFC. To find novel rare variants in IRF6 responsible for nonsyndromic OFC and TA, we performed targeted multiplex sequencing using molecular inversion probes (MIPs) in 1,072 OFC patients, 67 TA patients, and 706 controls. We identified 3 potentially pathogenic de novo mutations in OFC patients. In addition, 3 rare missense variants were identified, for which pathogenicity could not unequivocally be shown, as all variants were either inherited from an unaffected parent or the parental DNA was not available. Retrospective investigation of the patients with these variants revealed the presence of lip pits in one of the patients with a de novo mutation suggesting a Van der Woude syndrome (VWS) phenotype, whereas, in other patients, no lip pits were identified.
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Labio Leporino/genética , Fisura del Paladar/genética , Factores Reguladores del Interferón/genética , Anomalías Múltiples/genética , Quistes/genética , Predisposición Genética a la Enfermedad/genética , Humanos , Labio/anomalías , Mutación/genética , Mutación Missense/genética , Análisis de Secuencia de ADNRESUMEN
INTRODUCTION: The conditioning regimen used in cord blood transplantation (CBT) may significantly impact the outcomes. Variable pharmacokinetics (PK) of drugs used may further influence outcome. Individualized dosing takes inter-patient differences in PK into account, tailoring drug dose for each individual patient in order to reach optimal exposure. Dose individualization may result in a better predictable regimen in terms of safety and efficacy, including timely T cell reconstitution, which may result in improved survival chances. AREAS COVERED: Conditioning regimens used in CBT varies significantly between and within centres. For busulfan, individualized dosing with therapeutic drug monitoring has resulted in better outcomes. Anti-thymocyte globulin (ATG), used to prevent rejection and GvHD, significantly hampers early T-cell reconstitution (IR). Timely IR is crucial in preventing viral reactivations and relapse. By individudalizing ATG, IR is better predicted and may prevent morbidity and mortality. EXPERT OPINION: Individualization of agents used in the conditioning regimen in CBT has proven its added value. Further fine-tuning, including new drugs and/or comprehensive models for all drugs, may result in better predictable conditioning regimens. A predictable conditioning regimen is also of interest/importance when studying adjuvant therapies, including immunotherapies (e.g. cellular vaccines or engineered T-cell) in a harmonized clinical trial design setting.
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Sangre Fetal/trasplante , Enfermedad Injerto contra Huésped/prevención & control , Medicina de Precisión/métodos , Acondicionamiento Pretrasplante/métodos , Animales , Sangre Fetal/inmunología , Sangre Fetal/metabolismo , Sangre Fetal/fisiología , Predicción , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/metabolismo , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T/trasplante , Trasplante Homólogo/métodos , Resultado del TratamientoRESUMEN
DFNB1 is the most prevalent type of hereditary hearing impairment known nowadays and the audiometric phenotype is very heterogeneous. There is, however, no consensus in literature on vestibular and imaging characteristics. Vestibular function and imaging results of 44 DFNB1 patients were evaluated in this retrospective study. All patients displayed a response during rotational velocity step testing. In 65% of the cases, the caloric results were within normal range bilaterally. The video head impulse test was normal in all patients. In 34.4% of the CT scans one or more temporal bone anomalies were found. The various anomalies found, were present in small numbers and none seemed convincingly linked to a specific DFNB1genotype. The group of DFNB1 patients presented here is the largest thus far evaluated for their vestibular function. From this study, it can be assumed that DFNB1 is not associated with vestibular dysfunction or specific temporal bone anomalies.
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Pérdida Auditiva Sensorineural/diagnóstico por imagen , Pérdida Auditiva Sensorineural/fisiopatología , Hueso Temporal/diagnóstico por imagen , Vestíbulo del Laberinto/fisiopatología , Adolescente , Adulto , Niño , Preescolar , Conexina 26 , Conexina 30 , Conexinas/genética , Electronistagmografía , Movimientos Oculares , Femenino , Predisposición Genética a la Enfermedad , Movimientos de la Cabeza , Pérdida Auditiva Sensorineural/genética , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mutación , Nistagmo Fisiológico , Fenotipo , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
Seventeen obligate carriers from nine families with autosomal recessive Usher syndrome type I underwent otological, audiological, vestibular, and ophthalmological examination in order to identify possible manifestations of heterozygosity. Linkage studies were performed and six families showed linkage to chromosome region 11q13.5 while 3 families have so far failed to show linkage to the candidate regions. Eight obligate carriers had an abnormal pure-tone audiogram. Two different audiometric patterns could be distinguished when hearing loss was corrected for age and sex. Four carriers (24%) had significant sensorineural hearing loss (SNHL) which increased at higher frequencies. The other 13 carriers had SNHL of about 10 dB at 0.25 and 0.5 kHz, but less at higher frequencies. Vestibular findings were generally normal. Electro-oculography demonstrated a significant lower mean light peak/dark trough ratio in Usher type I carriers compared to normal control individuals. The methods used in this study were found not to be specific enough to clinically identify carriers of Usher type I syndrome. Nevertheless it is remarkable that a number of obligate carriers showed significant audiological and ophthalmological abnormalities.
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Cromosomas Humanos Par 11/genética , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva/genética , Heterocigoto , Retinitis Pigmentosa/genética , Adulto , Audiometría de Tonos Puros , Electrooculografía , Femenino , Fondo de Ojo , Genes Recesivos , Ligamiento Genético , Pérdida Auditiva/congénito , Humanos , Masculino , Persona de Mediana Edad , Linaje , SíndromeRESUMEN
OBJECTIVE: Evaluation of hearing impairment as a feature of the nonocular Stickler syndrome (type II) linked to COL11A2. STUDY DESIGN: Family study. METHODS: General, orthopaedic, ophthalmologic, and otorhinolaryngologic examinations were performed on 15 affected persons in a Dutch family. Audiograms were obtained and/or retrieved from elsewhere. Cross-sectional and longitudinal analyses were conducted on the hearing threshold (sensorineural component) in relation to the patient's age to evaluate whether hearing impairment was progressive. RESULTS: Mixed hearing loss, i.e., including a substantial air-bone gap of up to 20 to 60 dB, was present in six cases, concomitantly with a submucous or overt cleft palate in five of them. The audiograms in 14 evaluable cases showed the following types of threshold: U-shaped (n = 3), flat (n = 2), flat or gently (downward) sloping (n = 3), gently sloping (n = 3), or steeply sloping (n = 3). Cross-sectional analysis did not reveal any significant effect of age on sensorineural hearing impairment. CONCLUSION: In contrast to the classic Stickler syndrome (type I) with high myopia, this nonocular type shows a high prevalence of sensorineural hearing impairment. The mean sensorineural hearing threshold in our patients was about 40 dB HL (95% CI, 15-65 dB) and was liable to increase (presumably by presbycusis) by several tens of decibels at the highest frequencies. Given the tendency for otitis media to develop in many of these patients, appropriate otologic care is of major importance.
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Cromosomas Humanos Par 12/genética , Enfermedades del Tejido Conjuntivo/genética , Pérdida Auditiva Sensorineural/genética , Mutación/genética , Procolágeno/genética , Adulto , Factores de Edad , Análisis de Varianza , Audiometría , Umbral Auditivo , Conducción Ósea/genética , Fisura del Paladar/genética , Estudios Transversales , Progresión de la Enfermedad , Femenino , Ligamiento Genético/genética , Pérdida Auditiva Conductiva/genética , Humanos , Modelos Lineales , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Miopía/genética , Otitis Media/genética , Presbiacusia/genética , Prevalencia , SíndromeRESUMEN
Pendred syndrome is an autosomal recessive inherited disorder. Obligatory features are profound deafness in childhood and defective organic binding of iodine in the thyroid gland. Therefore, goiter is a common symptom. Hypoplasia of the cochlea is another feature. Recently, the gene for Pendred syndrome was identified. We describe a boy whose sensorineural hearing loss in both ears progressed rapidly from about 50 to 60 dB at the age of 3 years and 3 months to more than 100 dB at the age of 4 years and 4 months. This loss was preceded by a medical history of a progressive hearing loss. The progressive nature of the hearing loss motivated a search for the cause. Dysplasia of the cochlea and a widened vestibular aqueduct were found. The results of thyroid function tests were normal, but he had an elevated level of thyroglobulin. The diagnosis of Pendred syndrome was confirmed by the positive results of a potassium perchlorate test, indicating defective organic binding of iodine in the thyroid gland. It is possible that the widened vestibular aqueduct was responsible for the increase in the hearing impairment. Aside from the branchio-otorenal syndrome, Pendred syndrome is the only other known genetic disorder with a widened vestibular aqueduct. If a child has progressive sensorineural deafness and a widened vestibular aqueduct, it is important to consider a diagnosis of Pendred syndrome. A widened vestibular aqueduct may help to elucidate the pathophysiologic characteristics of hearing loss in these genetic types of deafness in childhood.
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Pérdida Auditiva Sensorineural/etiología , Acueducto Vestibular/patología , Preescolar , Cóclea/patología , Progresión de la Enfermedad , Pérdida Auditiva Sensorineural/fisiopatología , Humanos , Masculino , Síndrome , Tiroglobulina/sangre , Glándula Tiroides/fisiopatologíaRESUMEN
We present the results of the vestibular function tests of 35 patients who were selected for cochlear implantation. Vestibular function was evaluated with a caloric test and a velocity step test. The preimplant data were compared to those in previously reported series. Intracochlear implantation was performed in 25 patients. The vestibular complications encountered in this group are presented and discussed. Six patients had normal or residual (but substantial) vestibular function in the ear eligible for implantation. Vestibular function was preserved in 3 patients and was lost in 3 patients, in 1 case through an iatrogenic cause. We estimate the risk of losing vestibular function as a result of intracochlear implantation as between 50% and 60% on the basis of the present and previously reported data.
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Implantes Cocleares/efectos adversos , Reflejo Vestibuloocular/fisiología , Vestíbulo del Laberinto/lesiones , Vestíbulo del Laberinto/fisiología , Adulto , Pruebas Calóricas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Reflejo Anormal , Factores de RiesgoRESUMEN
An aetiological study was performed on 57 pupils at the deaf-blind department of the Institute for the Deaf at Sint-Michielsgestel, The Netherlands, in the school year 1998-1999 and on 49 deaf-blind pupils at the same department in the school year 1986-1987. The pupils were 5-20 years of age. In addition, the aetiologies were studied in 55 deaf infant pupils in 1998 and compared with those of 68 deaf infant pupils in 1988. Their age was 1-5 years. All the pupils showed hearing impairment with thresholds of >60 dB HL. Among the deaf-blind pupils and deaf infant pupils, there were several cases with rare hereditary syndromes. The prevalence of acquired causes of deafness, especially congenital rubella, had decreased over the years, whereas perinatal causes of deafness had increased. Chromosomal anomalies were found in 15% of the infant pupils in 1998. Over the study period, the percentage of pupils with multiple handicaps increased from 25 to 38%.
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Ceguera/epidemiología , Ceguera/etiología , Sordera/epidemiología , Sordera/etiología , Adolescente , Adulto , Distribución por Edad , Edad de Inicio , Audiometría , Umbral Auditivo , Ceguera/complicaciones , Niño , Preescolar , Sordera/complicaciones , Sordera/diagnóstico , Femenino , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/epidemiología , Pérdida Auditiva Sensorineural/etiología , Humanos , Lactante , Masculino , Países Bajos/epidemiología , Prevalencia , Factores de Riesgo , Muestreo , Instituciones Académicas , Distribución por SexoRESUMEN
Three cases of congenital cytomegalovirus (CMV) infection with long-term audiovestibular sequelae are presented. Case 1 had no hearing in one ear and severe progressive hearing loss in the other ear; he showed vestibular symptoms at the age of 4.5 years. Case 2 had severe but stationary hearing loss in one ear and showed hearing impairment symptoms in the other ear at 9-13 years of age. Case 3 did not have hearing impairment symptoms, or vestibular symptoms, but was found to have severe progressive hearing loss from the age of 15 months onwards, which led to profound deafness at the age of 2 years and vestibular areflexia at or before the age of 4 years. These cases may represent 3 symptomatically different types of delayed endolabyrinthine hydrops. Type 1 (ipsilateral hydrops) incorporates vestibular symptoms only because of a lack of hearing in the offending labyrinth. Type 2 (contralateral hydrops) incorporates hearing impairment symptoms only because of a lack of vestibular function on both sides and type 3 does not incorporate hearing impairment symptoms or vestibular symptoms (other than those relating to a complete lack of function). Given the present findings, those described by Weiss and Ronis (Trans. Pa. Acad. Opthalmol. Otolaryngol., 30 (1977) 52-54) in one case and other reported findings relating to histopathological or imaging methods in somewhat similar cases, it seems appropriate to include congenital CMV infection in the differential diagnosis of delayed endolymphatic hydrops.
Asunto(s)
Infecciones por Citomegalovirus/congénito , Hidropesía Endolinfática/virología , Trastornos de la Audición/virología , Enfermedades Vestibulares/virología , Adolescente , Umbral Auditivo , Niño , Preescolar , Sordera/virología , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Femenino , Estudios de Seguimiento , Pérdida Auditiva Bilateral/virología , Pérdida Auditiva Sensorineural/virología , Pérdida Auditiva Súbita/virología , Humanos , Lactante , Masculino , Nistagmo Optoquinético , Seguimiento Ocular Uniforme/fisiología , Reflejo Anormal/fisiología , Reflejo Acústico/fisiología , Movimientos Sacádicos/fisiología , Vértigo/virologíaRESUMEN
Six cases of the CHARGE association are described that were encountered consecutively at an institute for the deaf. Five of them showed external ear anomalies and according to expectations all of them showed some degree of hearing impairment: two had moderate mixed hearing loss; three had severe to profound sensorineural hearing loss; and one was completely deaf. In addition, they all had vestibular areflexia and the five cases examined with computer tomography of the petrosal bones showed aplasia of the semicircular canals. One case with poor visual acuity also showed subnormal optokinetic responses and horizontal pendular nystagmus during visual fixation. All these children were initially diagnosed as having severe psychomotor retardation, because of their failure to acquire speech and their delayed motor skill development. Given the fact that (mild) mental retardation was found in only one case, the delayed development could at least in part have been caused by vestibular areflexia. The vestibular findings support previously reported temporal bone findings that indicate dysplasia or aplasia of the superior part of the labyrinth. Early detection of the full extent of (multiple) sensory deficits is necessary in children with the CHARGE association who have similar abnormalities, because aggressive intervention and special educational support are likely to be of great benefit to sensorimotor development.
Asunto(s)
Anomalías Múltiples , Trastornos Psicomotores/etiología , Reflejo Vestibuloocular , Adolescente , Audiometría de Tonos Puros , Niño , Preescolar , Educación Especial , Femenino , Fijación Ocular , Trastornos de la Audición/diagnóstico , Humanos , Masculino , Nistagmo Patológico , Hueso Petroso/anomalías , Trastornos Psicomotores/diagnóstico , Trastornos Psicomotores/rehabilitación , Canales Semicirculares/anomalíasRESUMEN
An aetiological study was performed on 122 deaf pupils (57 aged < 20 years, 65 aged > 20 years) at the Institute for the Deaf in Sint-Michielsgestel, The Netherlands. Besides hearing impairment with thresholds of > 60 dB HL, all the participants had a mental handicap with a non-verbal IQ of 40-80. Sixteen per cent of them were of non-Dutch origin. The cause of hearing impairment was acquired in 48%, inherited in 17%, chromosomal in 4% and unknown in 30%. In comparison with other studies on the aetiology of childhood deafness, acquired causes predominated over inherited causes, which may be typical of deafness combined with a mental handicap. We found a significant predominance of non-Dutch pupils among the rubella aetiology cases and male predominance among the hearing impaired pupils in general.