Extension of the clinical and molecular phenotype of DIAPH1-associated autosomal dominant hearing loss (DFNA1).

In about 20% of non-syndromic hearing loss (NSHL) cases, inheritance is autosomal dominant (ADNSHL). DIAPH1 mutations define the ADNSHL locus DFNA1. We identified two new families with heterozygous truncating DIAPH1 mutations (p.Ala1210Serfs*31 and p.Arg1213*). In contrast to the extensively studied original DFNA1 family, hearing loss was not confined to low frequencies, but congenital manifestation and rapid progression were confirmed. In line with a recent unrelated study, we identified an association with thrombocytopenia, reclassifying DFNA1 as a syndrome. Consequently, we suggest to include the blood count into the initial clinical workup of patients with autosomal dominant hearing loss to guide the genetic diagnosis. We provide the first data on DIAPH1 expression in the organ of Corti, where it localizes to the inner pillar cells, at the base of the outer hair cells. Homozygous truncating DIAPH1 mutations located N-terminally to the DFNA1 mutations have recently been identified in autosomal recessive microcephaly. It is therefore noteworthy that we found DIAPH1 expression also in spiral ganglion neurons and in the barrier between the myelinating glia of the peripheral nervous system and oligodendrocytes that form the myelinating glia of the central nervous system (CNS).

[Do Early Cochlear-Implanted Toddlers Show a Better Speech Development than Later Implanted Children?] / Haben früh cochleaimplantierte Kinder eine bessere Sprachentwicklung als später versorgte Kinder?

Objective: Long term goal in early cochlea implantation in children without any additional disabilities is an age-appropriate speech development. Material and Methods: Speech development in deaf children with cochlear-implant(s) (n=60) was examined with the german language test battery SETK-2 ("Sprachentwicklungstest für 2-jährige Kinder") 2 years after first mapping of the speech processor. Results: More than 68% of the subjects show in all 4 subtests hearing-age equivalent results in receptive and expressive language. 12 children were additionally evaluated by chronological age. 4 of these children show age-appropriate results. There is no significant difference between the children implanted earlier in life (≤12 months) and later implanted children (≥13 months). But it must be kept in mind, that children who were implanted earlier show the same results at a younger age. The discrepancy between their chronological age and their speech development-age is smaller. Speech development in children who grow up bilingually was delayed in German. Conclusions: The results lead to the conclusion that the time of the cochlea implantation is crucial for further development of the children who were born deaf. Rehabilitation concepts have to put a special focus on children who grow up with more than one language.

[Receptive and expressive speech development in children with cochlear implant]. / Rezeptive und expressive Sprachentwicklung bei Kindern mit CI-Versorgung.

OBJECTIVE: This study's aim is the assessment of language development of children with Cochlea Implant (CI). It focusses on receptive and expressive language development as well as auditory memory skills. MATERIAL AND METHODS: Grimm's language development test (SETK 3-5) evaluates receptive, expressive language development and auditory memory. Data of 49 children who received their implant within their first 3 years of life were compared to the norms of hearing children at the age of 3.0-3.5 years. According to the age at implantation the cohort was subdivided in 3 groups: cochlear implantation within the first 12 months of life (group 1), during the 13th and 24th months of life (group 2) and after 25 or more months of life (group 3). RESULTS: It was possible to collect complete data of all SETK 3-5 subtests in 63% of the participants. A homogeneous profile of all subtests indicates a balanced receptive and expressive language development. Thus reduces the gap between hearing/language age and chronological age. Receptive and expressive language and auditory memory milestones in children implanted within their first year of life are achieved earlier in comparison to later implanted children. CONCLUSION: The Language Test for Children (SETK 3-5) is an appropriate test procedure to be used for language assessment of children who received a CI. It can be used from age 3 on to administer data on receptive and expressive language development and auditory memory.

[Phonological development in children with cochlear implant(s)]. / Phonologische Entwicklung bei Kindern mit Cochleaimplantat(en).

BACKGROUND: Normal-hearing children show signs of various phonological processes during language development. These processes represent simplifications of articulation, which are overcome at different time points. For the German language, there are currently no reliable data regarding whether these developmental stages also apply to deaf children with cochlear implants (CI). MATERIALS AND METHODS: Phonological development in deaf children with CI was examined and evaluated with the PLAKSS ("Psycholinguistischen Analyse kindlicher Sprechstörungen"). The results of this analysis (time of test 1 = T1, n = 33) were compared to those of a PLAKSS diagnostic evaluation performed 1 year previously (time of test 0 = T0, n = 31). RESULTS: At T1, 76 % of the whole group showed a phonological development that did not correspond to their hearing age (as measured from the time of the first CI implantation). The most frequently observed phonological processes were the reduction of consonant clusters and fronting. However, 83 % of the group had fewer phonological processes inappropriate to their hearing age at T1 than they did at T0. CONCLUSION: The phonological development of children with CI is not equivalent to their hearing age and is structured differently to that of normal-hearing children.

[Quality of universal newborn hearing screening results : Multicenter analysis of data recorded between 2009 and 2012 in four German states]. / Ergebnisqualität im universellen Neugeborenen-Hörscreening : Multizentrische Analyse von Daten der Jahre 2009 bis 2012 aus 4 Bundesländern.

BACKGROUND: Bearing in mind the impending evaluation of newborn hearing screening in Germany, this study investigated whether multicenter analysis of the screening results from four German states is possible and to what extent the results meet national quality and outcome criteria. MATERIALS AND METHODS: The screening data from 170 hospitals and a total of 533,150 newborns (21 % of all German newborns) from 2009 to 2012 were evaluated according to definite rules and analyzed in terms of averages, as well as over time. RESULTS: During the investigated period and averaged over the hospitals, the quality criteria "percentage of screened newborns" (91.4 %) and "percentage requiring further follow-up" (5.0 %), the "day of screening" (day 4), as well as the target parameter "age at diagnosis" (4.8 months) were not met. Steady improvements were observed over time: in the last year of the evaluation, 95.3 % of children were examined; only 4.8 % required follow-up and the age at diagnosis decreased to 4.2 months. On average, 83 % of the babies were screened before day 4. The steady reduction in variance of most of the variables from the participating hospitals indicates continual improvement. CONCLUSION: A multicenter analysis of screening data is possible and valid in the case of good quality data.

[Universal newborn hearing screening : Definition of uniform parameters by the Association of German Hearing Screening Centers as a requirement for nationwide evaluation with valid results]. / Universelles Neugeborenen-Hörscreening : Definition einheitlicher Parameter durch den Verband Deutscher Hörscreening-Zentralen (VDHZ) als Voraussetzung für eine flächendeckende Evaluation mit validen Ergebnissen.

BACKGROUND: Since 2009, all newborns in Germany have been entitled to universal neonatal hearing screening (UNHS). UNHS with tracking of test results leads to earlier detection of hearing disorders. The Association of German Hearing Screening Centers (Verband Deutscher Hörscreening-Zentralen, VDHZ) was founded to promote nationwide tracking, validity and quality control of UNHS results. OBJECTIVES: A comparable data structure in the different screening centers, with uniform definitions of primary parameters is essential for the nationwide evaluation of UNHS results. To address the question of whether a data structure with comparable definitions already exists or still has to be created, the existing structures and primary parameter definitions in the hearing screening centers should be investigated and compared. METHODS: A survey was conducted in all hearing screening centers to assess how data on the primary UNHS parameters defined in pediatric guidelines was gathered. In the case of discrepancies, uniform definitions were created. Finally, the practicability of these definitions was evaluated. RESULTS: Due to differing definitions of primary parameters, some of the data were not comparable between the individual centers. Therefore, uniform definitions were created in a consensus process. In the centers, the screening method, the two-step first screening and the result of the first screening now correspond to these uniform definitions. Other parameters, e.g. the total number of newborns, still vary widely, rendering the comparison of screening rates almost impossible. CONCLUSION: Valid evaluation of UNHS not only requires nationwide establishment of hearing screening centers, but also unified data structures and parameter definitions.

[Hearing impairment and language delay in infants: diagnostic and genetic]. / Kindliche Hör- und Sprachentwicklungsstörungen, Diagnostik und Genetik.

This article gives an overview on important aspects of hearing and language development of infants and toddlers. Newborn hearing screening is implemented in Germany for all infants since January 2009. The realization of early postnatal hearing screening is regulated by a publication of the "Gemeinsamer Bundesausschuss". It regulates the measurement method (TEOAE or AABR screening) and differs between healthy and sick newborns. It also rules the timetable of rescreening and if it still fails of paedaudiological follow up. The second part refers to objective and subjective assessment of hearing loss and different important issues of permanent childhood hearing impairment are discussed. Especially CMV infection by materno-fetal transmission and hereditary hearing loss is addressed in comparison to otitis media with effusion. Speech and language development in the first three years of live and the corresponding nomenclature is introduced in the last part. Different parent questionnaires are well established in evaluation of early language acquisition. An early diagnosis of language delay is possible and therapeutic measures can be established to prevent further social and psychological problems.

[Speech and general development in children receiving early cochlear implants]. / Sprachentwicklung und allgemeine Entwicklung bei Kindern mit früher Cochleaimplantation.

BACKGROUND: After cochlear implantation, most parents expect a normal speech and general development of their child. However, it remains unclear how quickly after early cochlear implantation these children can compensate for their deficits compared to normal-hearing children. METHODS: This study retrospectively analyzed ELFRA-1 questionnaire data from 40 children with borderline deafness or high-grade hearing loss (without other known impairments) who had undergone cochlear implantation at a university medical center before reaching 2 years of age. ELFRA-1 questionnaires were filled out parents assisted by specialists 12 months after implantation. Questions assessed the children's speech production and comprehension, as well as their use of gestures and fine motoric skills. RESULTS: At an average hearing-age of 12 months, the children achieved normal values in all of the subgroups that were comparable to those of 12-month-old children without hearing impairments. A significant correlation (p = 0.01) between the individual subgroups of the ELFRA-1 (speech production, speech comprehension, gestures and fine motor skills) was observed. Unilingual educated children performed significantly better overall. CONCLUSION: Within 12 months of receiving a cochlear implant, all children passed the four categories of the ELFRA-1. This demonstrates a rapid compensation of deficits in speech, motor skills and gesture development by children undergoing early cochlear implantation.

[Auditory synaptopathy/neuropathy: clinical findings and diagnosis]. / Auditorische Synaptopathie/Neuropathie: Klinik und Diagnostik.

Auditory synaptopathy/neuropathy (AS/AN) is a special subtype of sensorineural hearing disorders with heterogeneous phenotypes and underestimated incidence. AS/AN generally develops in infancy, occasionally in adulthood. Symptoms include fluctuating, mostly bilateral hearing loss and abnormally reduced speech comprehension, especially in noisy environments. Within audiological assessments, patients with AS/AN present otoacoustic emissions (TEOAE; DPOAE) and cochlear microphonics (CM), absence of stapedius reflexes (SR) as well as absent or pathologically altered auditory evoked brainstem potentials (ABR). Children with AS/AN cannot be identified within OAE-based newborn hearing screening programs. Clinical findings, transtympanic electrocochleography (ECoG) and further diagnostic tools permit further identification of individual characteristics. In individual cases conventional amplification and the use of FM systems may improve hearing and communication skills. If these interventions, accompanied by intensive hearing, speech and language therapy are unsuccessful, cochlear implants (CI) or alternative forms of communication may be useful options for rehabilitation.

Magnet dislocation following magnetic resonance imaging in cochlear implant users: Diagnostic pathways and managment.

OBJECTIVES: Although modern cochlear implants (CIs) are approved for magnetic resonance imaging (MRIs) adverse events still occur with unacceptable frequency. Methods: In this retrospective study, magnet displacement due to MRIs was analysed. Relevant factors e.g. symptoms during MRI, diagnostics, surgical intervention following the diagnosis and possible subsequent damage were assessed. RESULTS: 16 patients were enclosed. All patients complained about pain while the scan was conducted. Computed tomography (CT) scans of the temporal bone or X-rays of the skull were performed to confirm diagnosis. Artefacts on CT scans delayed immediate diagnosis in some cases. DISCUSSION: Despite various studies demonstrating the range of adverse events related to CIs following MRI, little information is available on diagnosis and radiologic recognition of magnet dislocation. In patients complaining about pain following an MRI scan an X-ray of the head should be performed immediately. Most adverse events occur in radiological centres without expertise in cochlear implants. CONCLUSION: Comprehensive training of patients, surgeons and radiologists is the most efficient tool to prevent damage to the CI and the patient. X-ray of the skull is suggested to be used as the method of choice in imaging.

[Development of a German version of the Functioning After Pediatric Cochlear Implantation (FAPCI) questionnaire]. / Entwicklung einer deutschsprachigen Version des Fragebogens Functioning After Pediatric Cochlear Implantation (FAPCI).

BACKGROUND: The Functioning After Pediatric Cochlear Implantation (FAPCI) instrument was recently developed to determine the communicative performance of 2-5-year-old prelingually deafened, cochlear-implanted children. Because of its high reliability and validity, as well as possible additional information compared with existing questionnaires, the 23-item parent-proxy questionnaire was translated from U.S. English to German prior to validation. MATERIAL AND METHODS: Initially, the German inventory was qualitatively developed by experts in audiology and speech pathology in collaboration with a professional American translator. Based on a sample of parents' responses, the outcome was quantitatively validated using psychometric methods (Cronbach's alpha, principal components analysis). Finally, the nomological validity was verified by correlating the overall FAPCI value with an external criterion (i.e., hearing age). RESULTS: For almost all age groups, Cronbach's alpha exceeded the minimum value of the original study (0.86). Principal components analysis revealed a two-factor solution (speech perception/production). The fitting of a nonparametric regression line to the data points showed that the total FAPCI score was positively associated with the time of implant use. CONCLUSION: The results show concordance between the German and the English versions of the FAPCI. The two instruments agree in reliability as well as in validity. The suitability of the German version in the clinical and therapeutic routine needs to be confirmed in further investigations.

[Experiments on prosody perception with cochlear implants]. / Experimente zur Perzeption prosodischer Merkmale mit Kochleaimplantaten.

BACKGROUND AND OBJECTIVE: Prosody has a myriad of linguistic functions and involves specific aspects of speech, such as stress, intonation and pauses. The underlying acoustic quantities (amplitude envelope, pitch frequency, and temporal structure) can be processed and transmitted by cochlear implants (CI) only to a limited extent. At present, no adequate tests are available in the German-speaking world for evaluation of the perception of prosodic elements. Different experiments have been conducted to address several prosodic cues, and the results are to be used as a basis for appropriate tests. METHODS: Various prosodic materials were used for the experiments. Discrimination was measured for minimal pairs differing in frequency and/or duration, accents in words and phrases, questions versus statements and phrasing. Measurements were performed in ten normal-hearing subjects and five with cochlear implants. RESULTS AND CONCLUSIONS: In all test modules, the subjects with normal hearing proved to have high discrimination rates of 96-100%. The test of word stresses was problematic because the results were influenced by different confounders. The other measurements did prove to be basically suitable for use in the subjects with implants. Early results revealed that the subjects with CI had few problems with prosodic cues based on the temporal structure, the outcome being similar to that of the subjects with normal hearing in these tests. In contrast, the performance of subjects with CI in perceiving prosodic cues based on amplitude variations and, especially, on alterations in pitch frequency was worse, even though some of them achieved very good results in these tests too. These preliminary tests can form the basis for development of a German-language prosody test battery with a limited number of subtests addressing different prosodic cues.

A novel locus for autosomal dominant, non-syndromic hearing impairment (DFNA18) maps to chromosome 3q22 immediately adjacent to the DM2 locus.

Investigating a large German pedigree with non-syndromic hearing impairment of early onset and autosomal dominant mode of inheritance, linkage to known DFNA loci was excluded and in a subsequent genomic scan the phenotype was mapped to a 10-cM interval on chromosome 3q22; a maximum two-point lod score of 3.77 was obtained for the marker D3S1292. The new locus, DFNA18, is excluded from neighbouring deafness loci, DFNB15 and USH3, and it overlaps with the recently described DM2/PROMM locus. As hearing loss has been described as one feature of the PROMM phenotype, the DFNA18 gene might also be responsible for hearing loss in DM2/PROMM.

Primary respiratory support in preterm infants with cleft lip and palate.

OBJECTIVE: Preterm infants with respiratory distress are routinely treated by application of nasal mask continuous positive airway pressure. In preterm infants with cleft lip and palate, nasal mask attachment is not feasible due to air leakage through the cleft defect. Here, we describe a modified continuous positive airway pressure application method that overcomes this problem. DESIGN AND SUBJECTS: Observation study, university neonatal intensive care unit. The neonates (n = 4) were between 28 and 33 weeks' gestation and weighed 1160 to 1680 g at birth. Immediately after birth, infants with unilateral cleft lip and palate (n = 3) were respiratory stabilised by a Medijet generator using a nasal tube. To minimise the pressure cap, hydrocolloid bandages were adhered over the total cleft defect. Immediately after orthodontic passive palatal plates insertion (within 27 hours of life), the nasal tube was removed and continuous positive airway pressure was applied through a nasal mask covering the complete nose of the infant. RESULTS: The system proved suitable for patients with unilateral cleft lip and palate for whom the generated nasal mask continuous positive airway pressure remained constant between 5 to 7 cm of water but failed in the patient with bilateral cleft lip and palate. None of the patients had to be ventilated due to respiratory failure, and all survived to discharge. CONCLUSION: Preterm infants with unilateral, but not bilateral cleft lip and palate, can be successfully stabilised using the described nasal mask continuous positive airway pressure system, thereby avoiding primary intubation and its associated risk of complications.

[Diagnosis and therapy of auditory synaptopathy/neuropathy]. / Diagnostik und Therapie der auditorischen Synaptopathie/Neuropathie.

Pathological auditory brainstem responses (lack of responses, elevated thresholds and perturbed waveforms) in combination with present otoacoustic emissions are typical audiometric findings in patients with a hearing impairment that particularly affects speech comprehension or complete deafness. This heterogenous group of disorders first described as "auditory neuropathy" includes dysfunction of peripheral synaptic coding of sound by inner hair cells (synaptopathy) and/or of the generation and propagation of action potentials in the auditory nerve (neuropathy). This joint statement provides prevailing background information as well as recommendations on diagnosis and treatment. The statement focuses on the handling in the german language area but also refers to current international statements.

[Cervical actinomycosis. A rare differential diagnosis of parotid tumor]. / Die zervikale Aktinomykose. Eine seltene Differentialdiagnose des Parotistumors.

Actinomycosis is currently an uncommonly diagnosed human disease. However, it can still complicate trauma to the respiratory and digestive tracts, including operative procedures. A patient with cervicofacial actinomycosis commonly gives a history of recent dental manipulation which usually, involves extraction of a mandibular molar. The common initial symptoms of infection--such as, sudden onset of cervicofacial pain, swelling, erythema, edema and suppuration--can be absent. Infection due to actinomyces is a well-known mimic of malignancy is clinical, radiological and pathological findings. In the case described a 65-year-old man had a mass in his right parotid area. Because of its painless rapid growth with infiltration of the mandible as demonstrated by clinical findings and CT and MRI scans, we established an initial diagnosis of salivary gland malignancy. Salivary gland biopsy then revealed a histological picture of infection due to actinomyces. Therapy was initiated with intravenous amoxicillin and sulbactam. After 20 days of treatment diseased soft tissues and bone were resected. To prevent a relapse the patient received oral clindamycin for 6 weeks. After a followup of two years, the patient has remained free of disease.

[Voice change and laryngeal obstruction caused by a median thyroglossal duct cyst]. / Stimmveränderung und laryngeale Obstruktion durch eine mediane Halszyste.

Thyroglossal duct cysts are common primary neck tumors, resulting from remnants of the ductus thyroglossus. They can occur at any point along the migratory path of the thyroid gland anlage until the 2nd or 3rd decade of life. The usual symptoms leading to the diagnosis are painless midline neck masses orfistulas. Despite their close proximity, the cysts normally do not affect the larynx. We report on the eighth case mentioned in the world literature of a thyroglossal duct cyst invading the larynx in a 62-year-old patient. Preoperatively, the voice of the patient sounded metallic, and the frequency of the voice field was reduced. Postoperatively, the voice onset was physiological, and the voice increased by an octave in the higher frequencies. The intonation of the voice was steady. The analysis of formants of the vowels "a" and "i" showed that the fourth formant of the vowel "i" was lower in frequency postoperatively.