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ABSTRACT: Despite known ototoxic effects of aminoglycoside (AG) antibiotics, audiological assessment is not routinely undertaken in UK CF patients. Consequently, the incidence of hearing loss is not well established. Objective: To document the incidence of hearing loss in cystic fibrosis (CF) children.
Hearing function of 45 children from Great Ormond Street Hospital was assessed using pure-tone audiometry up to 20kHz and DPOAEs up to 8kHz.
39/45 of participants had received intravenous (IV) AGs, 23 of which received repeated IV AGs every 3 months.
In this high exposure group, 8 (21%) had clear signs of ototoxicity; average 8-20kHz thresholds were elevated by ∼50dB and DPOAE amplitudes were >10dB lower at f2 3.2-6.3 kHz. The remaining 31/39 (79%) of AG exposed patients had normal, even exceptionally good hearing. The 21% incidence of ototoxicity we observed is substantial and higher than previously reported. However, our finding of normal hearing in children with equal AG exposure strongly suggests that other unknown factors, possibly genetic susceptibility, influence this outcome.
We recommend comparable auditory testing in all CF patients with high AG exposures. Genetic analysis may help explain the dichotomy in response to AGs found.
International journal of audiology 02/2011; 50(2):112-22. · 1.34 Impact Factor
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ABSTRACT: Ear involvement in the acute phase of Langerhans cell histiocytosis (LCH) is commonly seen and well documented, but the long-term sequelae are less well described, particularly in relation to hearing loss.
We investigated 40 patients with biopsy-proven multisystem LCH >5 years from the end of treatment, using detailed audiological assessment and CT/MRI imaging of the petrous temporal bones.
The incidence of ear involvement in the acute phase of disease was 70%. Fifteen of the 39 patients tested (38%) had residual permanent hearing loss at long-term follow-up.
The incidence of hearing loss is much higher than has previously been reported in LCH, and may reflect a referral bias of young (<2 years) and more complex patients to our tertiary centre. However, the hearing loss appears to be highly specific to this patient group when compared to other long-term survivors of childhood cancers, probably due to the propensity of LCH to involve the ears. We therefore recommend audiology testing as an important part of long-term follow-up for patients with multisystem LCH.
Pediatric Blood & Cancer 10/2009; 54(3):449-53. · 1.89 Impact Factor
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Detlef Bockenhauer,
Sally Feather,
Horia C Stanescu,
Sascha Bandulik,
Anselm A Zdebik,
Markus Reichold,
Jonathan Tobin,
Evelyn Lieberer,
Christina Sterner,
Guida Landoure, [......],
Mike Hubank,
Michael J Dillon,
Dirk Heitzmann,
Mauricio Arcos-Burgos,
Mark A Knepper,
Angus Dobbie,
William A Gahl,
Richard Warth,
Eamonn Sheridan,
Robert Kleta
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ABSTRACT: Five children from two consanguineous families presented with epilepsy beginning in infancy and severe ataxia, moderate sensorineural deafness, and a renal salt-losing tubulopathy with normotensive hypokalemic metabolic alkalosis. We investigated the genetic basis of this autosomal recessive disease, which we call the EAST syndrome (the presence of epilepsy, ataxia, sensorineural deafness, and tubulopathy).
Whole-genome linkage analysis was performed in the four affected children in one of the families. Newly identified mutations in a potassium-channel gene were evaluated with the use of a heterologous expression system. Protein expression and function were further investigated in genetically modified mice.
Linkage analysis identified a single significant locus on chromosome 1q23.2 with a lod score of 4.98. This region contained the KCNJ10 gene, which encodes a potassium channel expressed in the brain, inner ear, and kidney. Sequencing of this candidate gene revealed homozygous missense mutations in affected persons in both families. These mutations, when expressed heterologously in xenopus oocytes, caused significant and specific decreases in potassium currents. Mice with Kcnj10 deletions became dehydrated, with definitive evidence of renal salt wasting.
Mutations in KCNJ10 cause a specific disorder, consisting of epilepsy, ataxia, sensorineural deafness, and tubulopathy. Our findings indicate that KCNJ10 plays a major role in renal salt handling and, hence, possibly also in blood-pressure maintenance and its regulation.
New England Journal of Medicine 06/2009; 360(19):1960-70. · 53.30 Impact Factor
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ABSTRACT: GJB2 mutations account for approximately 50% of recessive non-syndromic deafness, with 35delG being the most prevalent. Homozygous 35delG mutations cause pre-lingual, non-progressive hearing loss that is detected on newborn hearing screening programmes. We present a sibling pair with homozygous 35delG mutations, who passed hearing tests in early infancy and developed progressive sensorineural hearing loss, one requiring a cochlear implant. These cases illustrate that deafness due to such mutations may have a late onset and consequently be missed on neonatal screening programmes and they may present an argument to consider neonatal screening for GJB2 mutations in order to aid early intervention.
International Journal of Pediatric Otorhinolaryngology 07/2006; 70(6):1119-24. · 1.17 Impact Factor
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ABSTRACT: We present the clinical and radiographic findings in a mother and son with a dominantly inherited mesomelic skeletal dysplasia almost identical to that described in a large Thai family by Kantaputra et al., in which ankle, carpal and tarsal synostoses were noted. The proband in the family is a 48-year-old woman with mesomelic limb shortening, most pronounced in the upper limbs. Her parents were of normal stature and build. Her 15-year-old son has similar mesomelic limb shortening, and in addition talipes equinovarus. Radiological examination showed severe shortening of the radius and ulna with bowing of the radius and dislocation of the radial head. Multiple carpal and tarsal synostoses were present and in addition, the talus and calcaneum were fused. In the original Thai family, linkage to chromosome 2q24-q32, which contains the HOXD cluster has been reported, and it is postulated that the phenotype may result from a disturbance of regulation of the HOXD cluster. Although linkage analysis was not possible in our family, molecular analysis was undertaken and HOXD11 was sequenced, however, no mutations were detected. This is only the second reported family affected with Kantaputra mesomelic dysplasia (MIM 156232), a distinct mesomelic skeletal dysplasia.
American Journal of Medical Genetics Part A 08/2004; 128A(1):6-11. · 2.39 Impact Factor
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ABSTRACT: To report left-sided peripheral vestibular failure as the cause of dizziness in a 12-year-old boy diagnosed as having chronic fatigue syndrome (CFS).
Retrospective case report with review of literature and discussion.
Tertiary children's hospital.
We recommend proper vestibular assessment for CFS patients presenting with dizziness, as effective treatment for peripheral vestibular disorder exists in the form of balance rehabilitation exercises.
International Journal of Pediatric Otorhinolaryngology 06/2002; 64(1):69-72. · 1.17 Impact Factor
