Michael Tsakanikos

Prevalence of GJB2 mutations in prelingual deafness in the Greek population

OBJECTIVE Mutations in the gene encoding the gap junction protein connexin 26 (GJB2) have been shown as a major contributor to prelingual, sensorineural, nonsyndromic, recessive deafness. One specific mutation, 35delG, has accounted for the majority of the mutations detected in the GJB2 gene in Caucasian populations. The aim of our study was to determine the prevalence and spectrum of GJB2 mutations in prelingual deafness in the Greek population. METHODS In a collaboration with the major referral centers for childhood deafness in Greece, patients were examined by an extensive questionnaire to exclude syndromic forms and environmental causes of deafness and by allele-specific polymerase chain reaction (PCR) for the detection of the 35delG mutation. Patients heterozygous for the 35delG mutation were further analyzed by direct genomic sequencing of the coding region of the GJB2 gene. RESULTS The 35delG mutation was found in 42.2% of the chromosomes in 45 familial cases of prelingual, nonsyndromic deafness (18 homozygotes and 2 heterozygotes) and in 30.6% of the chromosomes in 165 sporadic cases (45 homozygotes and 11 heterozygotes). Direct genomic sequencing in heterozygous patients revealed the L90P (2 alleles), W24X (2 alleles), R184P (2 alleles), and 291insA (1 allele) mutations. CONCLUSION Mutations in the GJB2 gene are responsible for about one third of prelingual, sensorineural, nonsyndromic deafness in the Greek population, and allele-specific PCR is an easy screening method for the common 35delG mutation.

Use of chloral hydrate as a sedative for auditory brainstem response testing in a pediatric population.

OBJECTIVE Chloral hydrate (CH) is an oral sedative widely used to sedate infants and young children during auditory brainstem response (ABR) testing. The aim of this study was to record effectiveness, complications and safety of CH as a sedative for ABR. METHODS From January of 2003 until December of 2007, 1903 children were tested for ABR, 568 of them being under the age of 6 months. CH (8%) was used for sedation at a dose of 40 mg/kg with a repeat dose, if necessary, for an adequate sedation, in 20-30 min. We recorded the effectiveness of CH as a sedative for ABR examination, as well as all complications related to the use of CH such as vomiting, rash, hyperactivity, respiratory distress and apnea. The statistical method used was the absolute and percentage frequency distribution of the occurrences. RESULTS Sedation with CH was necessary to perform testing in 1591 (83.6%) of the examined children. However, in the population of the examined infants, only 341 (60%) were sedated with CH, because the remaining 227 (40%) fell asleep by themselves. Complications included hyperactivity in 152 children (8%), minor respiratory distress in 10 children (0.4%), vomiting in 217 children (11.4%), apnea in 4 children (0.2%) and rash in 10 children (0.4%). The complications of hyperactivity, vomiting and rash resolved without any medical treatment. The apnea cases were managed effectively by supplying ventilation to the children via a mask in the presence of an anesthesiologist. CONCLUSIONS The use of CH at a dose of 40 mg/kg up to 80 mg/kg is safe and effective when administered in a setting with adequate equipment and the presence of well trained personnel.

Hearing loss in speech-language delayed children

An infant begins to communicate with his/her environment from the first months of life. However, true words do not appear until the age of 12-15 months, following a rather predictable sequence. Delay or failure of normal language development is not a rare situation in childhood and may be due to a variety of reasons. Among these, hearing undoubtedly plays a leading part in the language acquisition process. The purpose of this study was to assess the percentage of hearing-impaired children in a group of phenotypically healthy children presenting with speech-language delay. Between March 1993 and March 1999, 726 speech-language delayed children were examined in our department. In 72 of them, various diseases or syndromes had already been diagnosed and so they were excluded from the study. The remaining 654 apparently healthy children entered the study and underwent a thorough audiological assessment for determination of their hearing thresholds. Eighty-seven children (13.3%) showed various degrees of hearing loss. Most of them (55 children, 8.4%) suffered from sensorineural hearing impairment, while in 32 children (4.9%) a conductive hearing loss was discovered. The increased prevalence of hearing impairment found in our population mandates a thorough hearing evaluation for every case of speech-language delay, even for those children who show no evidence of other handicaps. This will help in the early diagnosis of hearing loss, allowing proper management to be instituted as early as possible.

Profound hearing loss and presence of click-evoked otoacoustic emissions in the neonate: a report of two cases.

Evoked otoacoustic emissions using click stimulus (cEOEs) were recorded in 450 consecutive children over a 12-month period. Of this group, 102 were babies treated in neonatal intensive care unit (NICU), classified as High Risk neonates according to the criteria of the Joint Committee on Infant Hearing. Audiologic examination in the latter was completed by auditory brainstem responses (ABR). Two of the neonates showed a profound hearing loss accompanied by strong cEOEs. The two cases are described and discussed together with the possibilities and limitations of transient evoked otoacoustic emissions in the auditory screening of the neonatal population. Despite the reported rare possibility of pure retrocochlear disorders, when cEOEs are used for neonatal screening purposes there is an actual risk of missing a profound hearing loss. Nevertheless, the use of cEOEs in combination with ABR may contribute to the differential diagnosis between cochlear and retrocochlear lesions.

Mastoid subperiosteal abscess in children: drainage or mastoidectomy?

OBJECTIVE To evaluate the management of mastoid subperiosteal abscess using two different surgical approaches: simple mastoidectomy and abscess drainage. METHOD The medical records of 34 children suffering from acute mastoiditis with subperiosteal abscess were retrospectively reviewed. In these cases, the initial surgical approach consisted of either myringotomy plus simple mastoidectomy or myringotomy plus abscess drainage. RESULTS Thirteen children were managed with simple mastoidectomy and 21 children were initially managed with abscess drainage. Of the second group, 12 children were cured without further treatment while 9 eventually required mastoidectomy. None of the children developed complications during hospitalisation, or long-term sequelae. CONCLUSION Simple mastoidectomy remains the most effective procedure for the management of mastoid subperiosteal abscess. Drainage of the abscess represents a simple and risk-free, but not always curative, option. It can be safely used as an initial, conservative approach in association with myringotomy and sufficient antibiotic coverage, with simple mastoidectomy reserved for non-responding cases.

Pseudohypacusis: the most frequent etiology of sudden hearing loss in children

Sudden hearing loss is a rare pathology in children. Several factors may be responsible for it although the exact etiology remains frequently undiagnosed. Among them, pseudohypacusis has been reported. However, the extent to which this pathology contributes to sudden hearing loss in children is unknown. This study evaluates the incidence of pseudohypacusis in children presented with sudden hearing loss. The medical records of 48 children presented to our department because of sudden hearing loss from 2002 to 2007 were reviewed. Diagnostic process included both subjective and objective audiological tests while organic hearing losses were further subjected to proper evaluation and treatment. 26 cases (54%) of pseudohypacusis and 22 cases (46%) of organic sudden hearing loss were diagnosed. In the pseudohypacustic group, girls outnumbered boys (16:10) and their mean age was 10.5 years. Pseudohypacusis represents the most frequent etiology of sudden hearing loss in children. Its detection is relatively simple using conventional audiological tests though in some cases even experienced clinicians may come to incorrect diagnosis.

Otoacoustic emission-based hearing screening of a Greek NICU population

The pressing need for early identification of hearing-disabled children has led to the development of several neonatal hearing screening programmes world-wide. Today otoacoustic emissions represent a widely used methodology for identification of neonatal hearing impairment. The purpose of the present study is to determine the sensitivity and specificity of click-evoked otoacoustic emissions (cEOAEs) in a Greek NICU population and compare the cEOAE data to the final hearing status of these children. A total of 438 ears of 223 neonates at high risk for hearing impairment were tested with both brainstem response audiometry (ABR) and cEOAEs. In 107 neonates the final hearing status was determined by using behavioural and playtone audiometry, at an age greater than 2 1/2 years. The sensitivity and specificity of the cEOAEs were found to be 90 and 92.4% when compared to ABR results and 90.9 and 91.1% when compared to the childrens hearing status, respectively. Click-EOAEs have been proved to be highly effective in determining whether or not hearing impairment really exists. Since conventional ABR does not meet the requirements for large scale screening programmes, the cEOAEs represent a reliable alternative.

Evaluation of acoustic reflectometry in detecting otitis media in children

Accurate detection of middle-ear effusion in children is not only useful but also necessary for diagnosis, management and follow-up of otitis media. A relatively new device, the Acoustic Otoscope (model 101, ENT Medical Devices) has been introduced for detecting middle-ear fluid in children. We tested 158 ears and the diagnosis was confirmed by acoustic admittance, acoustic reflex and pneumatic otoscopy. We propose 4.5 as a better breakpoint (the number on the vertical scale of the instrument which is the lower limit indicating middle-ear effusion) than 4.0 which is proposed by the manufacturer. In our results the 4.5 breakpoint maximizes both positive and negative predictive values (83 and 82% respectively) with satisfactory sensitivity and specificity (86 and 79% respectively) in detection of otitis media. Our clinical experience with this instrument, during the past 2 years, has led us to conclude that it is simple, non-invasive and objective. Unlike tympanometry, it requires no hermetic seal and is effective even if the child is crying. However, it is not sensitive enough when there are bubbles or negative pressure in the middle ear. When the user is aware of the flexibility of the instruments breakpoints (in our opinion this is an advantage of the device) for different uses and different populations, the reflectometer often reduces the need for tympanometry and confirms the otoscopic examination.

Prelingual Nonsyndromic Hearing Loss in Greece

Mutations in the gene encoding the gap-junction protein connexin 26 (GJB2) on chromosome 13q11 have been shown as a major contributor to prelingual, sensorineural, nonsyndromic deafness. One specific mutation, 35delG, has accounted for the majority of the mutations detected in the GJB2 gene in Caucasian populations and is one of the most frequent disease mutations identified so far with highest carrier frequency of 3,5% in the Greek population. In a collaboration with the major referral centers for childhood deafness in Greece, patients were examined by an extensive questionnaire to exclude syndromic forms and environmental causes of deafness and by allele-specific PCR for the detection of the 35delG mutation. The 35delG mutation was found in 32.1% of the alleles in 173 unrelated cases of prelingual deafness: 50 homozygotes and 11 heterozygotes. Individuals heterozygous for the 35delG mutation were further analyzed by direct genomic sequencing of the coding region of the GJB2 gene, which revealed R184P and 486insT mutations in single alleles. We conclude that the 35delG GJB2 mutation is responsible for one third of prelingual, sensorineural deafness in Greece, which is higher than the usually quoted 20% for Caucasian populations.

The change in the acoustic admittance phase angle: a study in children suffering from acute otitis media

Middle ear mechanics, in normal and in pathological conditions, is the subject of this research, with acoustic impedance measurements as the cornerstone. Previous studies have established the importance of admittance-phase tympanograms, mainly in frequencies higher than the conventional 226 Hz. The purpose of the present study was to record how acute otitis media (AOM) affects the middle ear system and function by evaluating the recordings of the change in phase angle parameter (Δθ) provided by an automated tympanometer using the sweep-frequency technique. Multifrequency and conventional tympanograms were obtained from 70 children suffering from AOM on consecutive visits. Values of Δθ from these subjects were compared to normative data previously acquired in our Department. It appears that changes in the mechanical status of the middle ear after AOM are reflected in abnormal Δθ values, despite the normal findings of conventional tympanometry. A positive history of AOM did not seem to influence the behaviour of the middle ear. In most cases, abnormal Δθ values coexisted with abnormal values of resonance frequency (RF), i.e. the frequency at which mass and stiffness of the middle ear are in balance, and total susceptance (ΔB) reaches 0mmhos and the converse. The Δ seems to be an important indicator of middle ear mechanical status that can record changes occurring in the system after AOM and undetected by low probetone tympanometry.