Arts syndrome or phosphoribosyl-pyrophosphate-synthetase-1 (PRPS1) deficiency is caused by loss-of-function mutations in the PRPS1 gene (Xq22.3). PRPS1 is an initial and essential step for the synthesis of the nucleotides of purines, pyrimidines, and nicotinamide. Classically, affected males present with sensorineural hearing loss, optic atrophy, muscular hypotonia, developmental impairment, and recurrent severe respiratory infections early in life. Treatment of a 3-year old boy with S-adenosylmethionine (SAM) replenished erythrocyte purine nucleotides of adenosine and guanosine, while SAM and nicotinamide riboside co-therapy further improved his clinical phenotype as well as T-cell survival and function.
Objectives Tubomanometry (TMM), described initially by Estève, is a relatively new manometric method for testing the eustachian tube function (ETF). This study presents the analysis of the measurement of ETF of healthy children by TMM, which has, to date, not been properly evaluated. The objectives of the study were to establish normative data for TMM and to demonstrate TMM as a reliable and valid method for measuring ETF in children. Design The evaluation, after initial power analysis, comprised 35 children from 6 to 15 years of age with an intact tympanic membrane, no severe ET dysfunction, and less than three inflammations of the middle ear in their medical history. TMM was performed twice at three pressure levels for both ears. Statistical assessment of the various parameters of TMM was performed with emphasis on the R value and possible age dependency. Results The 90th percentile for the R value was calculated to be 1.12. No clinically relevant age effect regarding the use of TMM as a screening method for children was found. Healthy children showed an opening within normal limits for the so-called R value in 88%; a delayed opening was measured in 6%, and rarely no opening was measured in 2%. Conclusions TMM is a reliable tool for measuring ETF in children. The normal limit for the R value should be set at 1.12. The proposed measuring algorithm and results can be used to calculate sensitivity and specificity in a future study.
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominantly inherited disorder characterized by dysphagia, ptosis, and proximal limb weakness and is caused by germline mutations (triplet repeat expansions) in the polyadenylate binding protein nuclear 1 (PABPN1) gene.To describe a 70-year-old female patient with OPMD on the clinical and molecular genetic level and to develop a rapid and efficient molecular genetic screening method to study large patient groups.Detailed family history and clinical assessment of the OPMD patient were followed by mutation analysis of the PABPN1 gene by direct DNA sequencing and by our newly developed method, fluorescent PABPN1 polymerase chain reaction (PCR) product (flPPP) method. A cohort of 50 healthy Swiss probands was screened using the flPPP to assess the frequency of the (GCG)7 allele in the Swiss population. Cricopharyngeal myotomy was performed as treatment for dysphagia.A heterozygous (GCG)9 triplet repeat expansion in PABPN1 was identified. Since the family history proved to be negative, the mutation is likely to have occurred de novo. The frequency of the (GCG)7 allele among healthy Swiss controls amounted to 1%. The flPPP method showed a sensitivity and specificity of 100%. Two years after cricopharyngeal myotomy, the patient is still relieved of dysphagia.An otolaryngologist should include OPMD in the differential diagnosis of a patient presenting with dysphagia, as this symptom can be the first sign of the disease and family history can be negative. Molecular genetic testing represents a highly accurate and rapid way to confirm the clinical diagnosis of OPMD. Cricopharyngeal myotomy relieves the patient of dysphagia in the majority of cases.
Objective: Identification of the causative mutation using next-generation sequencing in autosomal-dominant hereditary hearing impairment, as mutation analysis in hereditary hearing impairment by classic genetic methods, is hindered by the high heterogeneity of the disease. Patients: Two Swiss families with autosomal-dominant hereditary hearing impairment. Intervention: Amplified DNA libraries for next-generation sequencing were constructed from extracted genomic DNA, derived from peripheral blood, and enriched by a custom-made sequence capture library. Validated, pooled libraries were sequenced on an Illumina MiSeq instrument, 300 cycles and paired-end sequencing. Technical data analysis was performed with SeqMonk, variant analysis with GeneTalk or VariantStudio. The detection of mutations in genes related to hearing loss by next-generation sequencing was subsequently confirmed using specific polymerase-chain-reaction and Sanger sequencing. Main Outcome Measure: Mutation detection in hearing-loss-related genes. Results: The first family harbored the mutation c.5383+5delGTGA in the TECTA -gene. In the second family, a novel mutation c.2614-2625delCATGGCGCCGTG in the WFS1 -gene and a second mutation TCOF1- c.1028G>A were identified. Conclusion: Next-generation sequencing successfully identified the causative mutation in families with autosomal-dominant hereditary hearing impairment. The results helped to clarify the pathogenic role of a known mutation and led to the detection of a novel one. NGS represents a feasible approach with great potential future in the diagnostics of hereditary hearing impairment, even in smaller labs.
This article describes the technique of ultrasound-guided core-needle biopsy in the head and neck, and also warns of its risks. In contrast to fine-needle aspiration, this minimally invasive procedure has the advantage of supplying a histological specimen rather than a cytological smear. Therefore, it could be used as an additional diagnostic tool in the investigation of head and neck lesions, and can be carried out within the out-patients clinic.
Abstract Background and objective: X-linked hypophosphataemic osteomalacia is the most common of the genetically determined forms of osteomalacia. The occurrence of hearing loss in X-linked hypophosphataemic osteomalacia has been known since 1984. However, observations on the progression of such hearing loss, and suggestions regarding possible therapy, have not previously been published. Methods: Case report of a patient with X-linked hypophosphataemic osteomalacia and hearing loss, with three years' audiological follow up, description of empirical therapy and literature review. Results: The patient presented with fluctuating hearing. An audiogram showed mild to severe sensorineural hearing loss mainly in the low and high frequencies. A temporary improvement of 20–40 dB after steroid therapy was observed. Four weeks later, hearing had deteriorated again, mainly in the low frequencies. After one year of fluctuating hearing levels, stabilisation occurred. Conclusions: In X-linked hypophosphataemic osteomalacia, hearing loss occurs predominantly in the low and high frequencies. The hearing loss type and progression pattern point to an endolymphatic hydrops as the pathogenetic mechanism. Steroid therapy may be of some benefit.
The ageing process of hearing is well known. Age-dependent normative data are established for pure tone audiometry. It seems logical to suppose that the peripheral vestibular system undergoes a similar ageing process. To support this hypothesis we investigated subjects aged 50-82 with presbyacusis demonstrated by pure tone audiometry. Asymmetry of the peripheral vestibular system was ruled out by symmetrical thermal excitation rate. Slow-phase velocity of nystagmus induced by rotating-chair stimulation was compared with pure tone audiometry. We found no significant correlation and thus our approach failed to bear out the hypothesis.
Abstract Background: As the trend of refractive lens exchange for presbyopia continues to grow, our case report shows the first occurrence of an acute bilateral outer retinopathy following uncomplicated sequential clear lens extraction in an otherwise healthy individual. Case presentation: A 54-year-old male without significant medical history benefited from a sequential bilateral lens exchange for presbyopia. He then experienced a rapid vision loss in both eyes, accompanied by photopsias and myodesopsias, with symptoms appearing respectively 4 and 3 weeks after the surgeries. Multimodal imaging revealed a fulminant outer retinopathy, leading to a total loss of light perception within a few days. Immediate intravenous corticoid therapy was administered, permitting to recover a small area of central visual function in both eyes, enabling shape and color distinction. The primary diagnostic hypothesis is a presumed autoimmune retinopathy, triggered by the cataract extraction, while an alternative diagnosis could be a toxic reaction secondary to the use of intracameral cefuroxime and lidocaine during the surgery. Conclusion: In this report, the authors describe the first recorded instance of outer retinopathy following cataract surgery. This occurrence raises the possibility of auto-immunization leading to retinal atrophy and vision loss as a potential outcome after undergoing cataract surgery.
