Hypogonadotrophic hypogonadism associated with prelingual deafness due to a connexin 26 gene mutation.

In Mediterranean countries, almost half the incidence of non-syndromic congenital hearing loss is caused by mutations in the gap junction (GJ) connexin 26 gene (GJB2/DFNB1 locus). In this form of deafness the cochlear defect is usually isolated. We describe here the first case of hypogonadotrophic hypogonadism in association with this particular cochlear defect. The male patient had moderate deafness inherited from his deaf parents. All family members had a homozygous 35delG mutation in the connexin 26 gene. This mutation accounts for 70% of all connexin 26 gene mutations. The patient was referred to a paediatric endocrinology unit at 11 years of age for moderate growth retardation. Growth rate was normal until 11 years. The patient then presented delayed puberty (testicular volume 4 ml, penis length 4 cm) and did not undergo the usual pubertal growth spurt. LH and FSH secretory responses to GnRH at the age of 14.5 years (bone age 13.5 years), were: LH baseline level 1.1 IU/l, peak 34 IU/l; FSH baseline level 1.8 IU/l, peak 5.7 IU/l. Testosterone concentration was <0.11 ng/ml. From 11 to 14 years old, testosterone concentration ranged from 0.11 to 0.2 ng/ml. Anti-Mullerian hormone (AMH) level was 38.6 ng/ml (normal for Tanner stage I), cortisol 109 ng/ml, and ACTH 37 pg/ml., Karyotype was 46 XY. On MRI analysis, the anterior pituitary and olfactory bulbs were normal. These data were consistent with partial hypogonadotrophic hypogonadism of hypothalamic origin, and the patient was treated with testosterone. This report supports the possible involvement of connexins in puberty initiation. Connexins may play a part in the co-ordination and synchronisation of GnRH release.

Connexin 26 gene mutations in congenitally deaf children: pitfalls for genetic counseling.

OBJECTIVE: To evaluate difficulties encountered in genetic counseling in deaf children carrying connexin 26 gene (CX26 or GJB2) mutations. DESIGN: Prospective study. SETTING: Outpatients, tertiary referral center. PATIENTS: Ninety-six unrelated deaf children in whom CX26 mutations had been detected consecutively. Children were recruited to a center for genetic counseling for deaf children, and all had congenital deafness, sporadic or familial. RESULTS: In 63 children, deafness was clearly a DFNB1 form with autosomal recessive inheritance: 47 of the 63 were homozygous for the most frequent mutation, the deletion of G at position 35 (35delG); 16 of 63 carried on both alleles of CX26 frameshift or stop mutations, or missense mutations affecting a critical region of the gene. In 33 of 96 children, genetic counseling was difficult: 21 of 33 had a single mutation detected, 11 of 33 had new missense mutations or mutations whose pathogenicity remains debated in the literature, and 1 of 33 had a genotype with both a recessive mutation (35delG) and a mutation acting as a dominant mutation. CONCLUSIONS: Interpretation of results for the molecular diagnosis of mutations in the connexin 26 gene is difficult in almost one third of cases. Close collaboration between geneticists familiar with deafness and otolaryngologists is essential to provide a high standard of genetic advice.

Audiophonological results after cochlear implantation in 40 congenitally deaf patients: preliminary results.

The aim of this study is to evaluate the prognostic factors of audiophonological results in cochlear implant in congenitally deaf patients. Between 1991 and 1996. 40 congenitally deaf children underwent cochlear implantation in our department, at an average age of 7 years (median: 5 years). The results of speech therapy were evaluated with a mean follow-up of 2 years and were classified according to four criteria: perception of sound, speech perception, speech production and the level of oral language. For each criterion, a score was established ranging from zero to four. These scores were weighted according to age such that the results before and after implantation only reflected the changes related to the implantation. The prognostic factors for good results were: a good level of oral communication before implantation, residual hearing, progressive deafness and implantation at a young age. On the other hand, poor prognostic factors were: the presence of behavioral disorders and poor communication skills prior to implantation. Overall, the major prognostic factor for a good outcome appeared to be the preoperative level of oral language, even if this was rudimentary.

Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect: implications for genetic counselling.

BACKGROUND: DFNB1, the locus of an autosomal recessive form of deafness due to mutations in the connexin-26 gene (CX26 or GJB2) is one of the most frequent hereditary defects in human beings. To date, no clinical characterisation of the DFNB1 inner-ear defects has been reported, which precludes the provision of prognostic information and genetic counselling. METHODS: We enrolled, in a prospective study, 140 children from 104 families affected by sensorineural deafness with various degrees of hearing loss. The children either belonged to a family affected by autosomal recessive deafness (DFNB family) or represented sporadic cases. We searched for mutations in the 5' non-coding exon and in the coding region of CX26. Audiometric and radiological features were investigated and compared in deaf children with and without CX26 mutations. FINDINGS: CX26 mutations were present in 43 (49%) of the 88 families with cases of prelingual deafness versus none of the 16 families with postlingual forms of deafness (p<0.01). The inner-ear defects of 54 prelingually deaf children with biallelic CX26 mutations were compared with the defects in 57 prelingually deaf children without CX26 mutations. DFNB1 deafness varied from mild to profound, associated with sloping or flat audiometric curves and a radiologically normal inner ear. Hearing loss was not progressive in 11 of 16 cases tested, and variations in the severity of deafness between siblings were common. INTERPRETATION: The characteristic audiometric and radiological features of DFNB1 should be the reference used to guide the investigation, by CX26 molecular diagnostic tests, of deaf children with a compatible phenotype. Prognostic information can now be given to families: the hearing loss in DFNB1 deafness is non-progressive in most cases, at least up to young adulthood. An important element for genetic counselling is that the severity of hearing loss due to DFNB1 is extremely variable and cannot be predicted, even within families.

Role of modern imaging technology in the implementation of pediatric cochlear implants.

Since 1989, 40 patients have received cochlear implants in our institution. Over the past 2 years, 17 children among these patients have undergone radiographic assessment combining magnetic resonance imaging (MRI) and high-resolution computed tomography (CT) scanning. Imaging is not essential, and is only used after assessment by a multidisciplinary team. However, the imaging results influence the choice of implant, and sometimes the side to be implanted. The first study is always CT, as it detects congenital abnormalities, and for children with a history of bacterial meningitis, it can detect signs of labyrinthine ossification that contraindicates or complicates cochlear implantation. These signs are not always visible with tomodensitometry, especially when fibrosis within the canal has not yet ossified. This examination also provides for postoperative confirmation of implant position in case of failure or complication. Over the past 3 years, MRI has been combined with tomodensitometry, especially with children having a history of meningitis. This examination provides a basis for evaluating the liquid nature of the labyrinth. A GE Signa 1.5-T unit was used by the authors, employing sequences of volumetric acquisition (steady state free precision with 1.5-mm image slices and an angle of 15 degrees to 35 degrees). Hence, modern imaging plays an important role when the decision to implant has already been made, particularly in the case of profoundly deaf children. We always use MRI in combination with a CT scanner in children with a history of meningitis.

[Role of modern imaging (tomodensitometry and MRI) in cochlear implantation in children]. / Place de l'imagerie moderne (tomodensitométrie et I.R.M.) dans l'implantation cochléaire chez l'enfant.

Since 1989, 40 patients have received implants in the O.R.L. ward of the Hôpital d'Enfants Armand Trousseau (Paris). Over the past 2 years, 17 children have undergone radiological assessment combining M.R.I. anf high resolution C.T scanning. Imagery is not the essential stage, and is only used after assessment by a multidisciplinary team. However, the imagery results influence the choice of implant, and sometimes the side to be implanted. C.T is always the first stage as it detects congenital abnormalities, and, for children with a history of bacterial meningitis, it can detect signs of labyrinthine ossification which contraindicate cochlear implantation. These signs are not always visible using tomodensitometry, especially when fibrosis within the canal has not yet ossified. This examination also provides for post-operative confirmation of implant position in case of failure or complication. Over the past 3 years, Magnetic Resonance Imagery has been combined with tomodensitometry, especially with children having a past medical history of meningitis. This examination provides a basis for evaluating the liquid nature of the labyrinth. A G.E. Sygna 1.5 T was used by the authors, employing sequences of volumetric acquisition (S.S.F.P. with 1.5 mm image slices and an angle of 15 to 35 degrees). Hence, modern imagery plays an important role when the decision to implant has already been taken, particularly in the case of profoundly deaf children. M.R.I. is always used in combination with a scanner in cases involving children with a past medical history of meningitis.

[Auditory evoked potentials by electric stimulation of the cochlea]. / Potentiels évoqués auditifs par stimulation électrique de la cochlée.

The recording of auditory brain stem potentials evoked by electrical stimulation of the cochlea is a part of our assessment protocol before pediatric cochlear implantation. It constitutes an objective and reproducible method to estimate the stimulability of the auditory system for candidates to cochlear implant. Ten children, aged from 3 to 12 years, with deep deafness of the 2nd and 3rd group with no response to ABR, undergone electric stimulation of the cochlea. All patients were anesthetized and paralyzed. Electric pulses are delivered by a cochlear stimulator, through a transtympanic needle electrode, placed in the promontory. We record responses on a Medelec "Saphire" computer. One of the main problem we try to solve is the stimulus artefact which occurs during the first ms. The other one is to be sure that the recorded responses are corresponding to the neural activity of the auditory nerve and the brainstem auditory pathway.

[Sudden isolated cochlear deterioration in children]. / Détériorations cochléaires brusques, isolées, chez l'enfant.

Within a general study on the long-term outcome of tonal auditive thresholds in children, the authors analyzed 26 cases of sudden onset cochlear deterioration (unilateral or bilateral deficiency without former pathology, or sudden worsening of a known perception loss). The patients were hospitalized and followed the standard treatment course for sudden hearing loss. The characteristics of the former hearing deficiency, the original causes of the deafness or the sudden deterioration, and the short, medium and long-term audiometric thresholds were studied to determine possible prognostic factors. Sudden deafness, fluctuating hearing loss, progressive hearing loss, sudden cochlear deteriorations and the nosologic situation do not appear to have much signification in this poorly defined field of perception deficiency in children. Certain terminologies or classifications would appear simply to hide our ignorance of the true mechanisms underlying these problems.

[Audiophonologic aspects of the decision and follow-up of cochlear implants in children]. / Aspects audiophonologiques de la décision et du suivi de l'implant cochléaire chez l'enfant.

Based on the audiologic, audioprosthetic, psychological and orthophonic criteria involved in the decision for a cochlear implant in 16 children (age 5 to 18), a protocol including 10 criteria was developed for children with severe deafness and a low to very low level of oral language acquisition. The importance of the motivation of the family, their capacity to become implicated and their desire to listen to the child and communicate orally with him, as well as the role of the specialist teachers were emphasized. In this series of 16 children the results of the implantation work-up lead to only 9 cases of implantation.

[Cochlear implants in children]. / Les implants cochléaires chez l'enfant.

The development of surgically implantable hearing aids that are placed directly in the cochlea where they send electrical impulses to the cochlear nerve is a major break-through for patients whose hearing loss is so severe as to make conventional electroacoustic hearing aids ineffectual. Initially used only in adults, this method has gradually been extended to pediatric patients. To benefit from a cochlear implant, the patient must fulfill a number of criteria which are specified in this article. Following preoperative investigations, the decision is taken during a meeting of all the care providers involved, i.e., the surgeon, ENT phoniatrist or audiophonologist, hearing aid specialist, special education provider, speech therapist, psychologist, and other members of the health care staff. Team work is thus essential both before and after the procedure. The implant selected can be intracochlear or extracochlear and single-channel (one electrode) or multi-channel (several electrodes). Each team selects the implantation technique and type of implant they use according to their preferences and specific criteria. The authors use a multi-channel intracochlear system except in the rare instances where complete ossification of the cochlea requires use of an intracochlear mono-channel system. They have inserted implants in 29 patients to date. The cochlear implant has unquestionably had a significant impact of the life of these patients.

[Congenital sensorineural deafness and associated syndromes]. / Surdités de perception congénitales et syndromes associés.

The etiology of perceptive deafness, especially the congenital variety, requires investigation. The presence of a variety of signs associated with deafness constitutes an "associated syndrome" and helps to define a possible genetic origin. These syndromes only represent a small percentage of overall causes of deafness in children, since at most they account for only 10% of cases. Certain syndromes are encountered more often or are well known, others are extremely rare or have only been described recently. The authors report six of these very rare syndromes discovered among their patients: a KID syndrome, a Leopard syndrome, a Norrie syndrome, a Jervell and Lange Nielsen syndrome, a recently described entity called CEE with deafness and an External Neuro-Cochleo-Pancreatic syndrome which would not appear to have been previously described.

[Development of tone curves in sensorineural deafness in children]. / Evolution des courbes tonales dans les surdités de perception de l'enfant.

The authors reviews 239 cases of child sensorineural deafness (478 ears studied both separately and in correlation with the controlateral ear) to try and identify the evolutionary trend of the tone curves throughout the follow-up period, which spanned nearly 20 years in some cases. The difficulties encountered in this study were due to several factors, namely the problem involving very accurate assessment in very young children, the high incidence of tubotympanal disease in the very young, the hard to obtain definition and quantitative evaluation of the notion of progressiveness, as well as the need to analyze the evolutionary patterns in global terms (mean hearing loss), from one frequency to the next and from one ear to the other, since such tone loss patterns are not always symmetric. The authors state their opinion derived from a large number of cases regarding a situation, which characterizes a relatively frequent (over 25% of cases) aggravation of perceptive hearing loss in children.

[The dilated vestibular aqueduct syndrome]. / Le syndrome de l'aqueduc du vestibule dilaté.

The authors analyse the clinical, radiological and audiometric findings in a population of 89 ears of 49 patients. There was no correlation between bone malformation and auditory deficit which was often profound. This anomaly occurs during the 7th week of embryogenesis and represents one facet of the dysplasia of Mondini.

Studies on an isolated West Indies population. III. Epidemiologic study of sensorineural hearing loss.

An epidemiologic study of hearing loss was undertaken on a small Caribbean island and revealed a high frequency of abnormal audiograms among the population of French origin. Since there is no clear-cut discrimination between hypoacusis and normal hearing, but rather a continuous spectrum, the degree of hearing loss was quantified by an audiometric index, using the results of audiograms performed on 70% of the inhabitants. No environmental factors could be identified, although the effect of such factors is highly suggested by several observations of deafness aggravated by, or appearing after, a small dose of ototoxic antibiotics, and also by a strong residual age effect after correction for physiological presbyacusis. Hearing loss was found to be sparsed all over the island. Familial aggregation was noticed for several severe cases.

[Value of the study of cochlear microphonic recordings in deep and severe deafness]. / Intérêt de l'étude du microphonique cochléaire dans les surdités sévères et profondes.

A study was conducted to assess the contribution of cochlear microphonic potential recordings during electrophysiologic audiometry examinations. Amplitude of microphonic recordings were correlated with the degree of deafness, its etiology, and the prosthetic prognosis in 38 electrocochleographic examinations. Preliminary results are analyzed.

[1-stage operation in major aplasias of the ear. Value of combined plastic and functional intervention]. / Le premier temps opératoire dans les aplasies majeures de l'oreille. Intérêt d'une intervention conjointe plastique et fonctionnelle.

In spite of imperfections, combined functional and plastic surgery is of value of treating major aplasias of the ear. The two operative procedures can be performed by the same surgeon or the same team when the child has reached 5 to 6 years of age. The technique involves the use of sliding pedunculated flaps, with rotation in the auricular region, and the employ of conventional otologic microsurgical methods (homograft, moulded temporal aponeurosis). Results in 48 cases demonstrated auditory improvement of more than 20 decibels in 47-5 p. cent of cases, and 30 to 40 decibels in 20.8 p. cent.