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Neonatal hearing screening has been developped in a large number of countries. The rational to build such nationwide programs is robust. The prevalence of hearing impairment of various etiologies is high (1/1,000), diagnosis of hearing impairment in infants is uneasy and is made most of the time after the age of 18 months when treatment is less efficient and, last, appropriate test to screen for hearing impairment are available: Otoacoustic Emission and Auditory Evoked Potential. In France the screening is organised at the regional level. The organization of such a program is complexe. Midwifes and nurses should be trained to informed the parents and to perform the test. If the test is abnormal the infant will be oriented to a specialzed department of pediatrics for appropriate diagnosis and treatment.Le dépistage néonatal de la surdité.Le dépistage néonatal de la surdité doit être systématiquement proposé aux familles en maternité depuis l’arrêté du 23 avril 2012. La justification de ce dépistage repose sur une prévalence élevée de la surdité (autour de 1/1 000), l’existence de tests de dépistage fiables que sont les oto-émissions acoustiques et les potentiels évoqués auditifs automatisés, l’existence d’un retard important au diagnostic en l’absence de dépistage, et le bénéfice prouvé d’une prise en charge précoce. Le dépistage néonatal de la surdité permet également un bilan étiologique précoce. L’organisation actuelle de ce dépistage repose sur les Agences régionales de santé, qui s’appuient, selon les régions, sur les réseaux de périnatalité ou les centres régionaux de dépistage néonatal. La formation du personnel de maternité concerne le circuit du dépistage néonatal, l’utilisation des appareils et l’information aux familles. Le discours doit être standardisé : il s’agit de réaliser des tests d’audition, qui peuvent ne pas être concluants et sont alors répétés le lendemain ; si besoin, on revérifiera l’audition après la sortie de la maternité. En aucun cas, un diagnostic de surdité ne doit être évoqué en maternité. En cas de test anormal, une étape de re-test est prévue dans le premier mois après la naissance, avant d’adresser l’enfant dans un centre de diagnostic et de prise en charge de la surdité, où l’annonce diagnostique et la prise en charge sont multidisciplinaires. L’organisation régionale du dépistage néonatal de la surdité a conduit à une hétérogénéité des organisations et à l’absence de données nationales annuelles. Une enquête de 2015 (Santé publique France) a montré que plus de 94 % des nouveaux nés sont dépistés, avec un taux de surdité de 0,9 pour 1 000.

International audience; Reunion Island is a French oversea department in the Indian Ocean with 1.6/1000, an estimated prevalence of deafness that is almost double as compared to the mainland France. Twelve children having isolated bilateral prelingual profound deafness along with motor delay attributed to vestibular areflexia were enrolled. Their mean walking age was 19 months. Electroretinography and temporal bone CT-scans were normal in all cases. A novel homozygous frameshift lipoma HMGIC fusion partner-like 5 (LHFPL5) variant c.185delT p.(Phe62Serfs*23) was identified using whole-exome sequencing. It was found in seven families. Four patients from two different families from both Reunion Island and mainland France, were compound heterozygous: c.185delT p.(Phe62Serfs*23) and c.472C > T p.(Arg158Trp). The phenotype observed in our patients completely mimics the hurry-scurry (hscy) murine Tmhs knock-out model. The recurrent occurrence of same LHFPL5 variant in Reunion Island is attributed to common ancestor couple born in 1693.

OBJECTIVE To analyze clinical signs and better define the underestimated long-term pain after implantation, to discuss etiological hypothesis, and to propose our department treatment algorithm and results. STUDY DESIGN AND SETTING Retrospective review of children implanted with complaints of atypical pain in the area of device implantation, not in the immediate postoperative period, more than or equal to 4 on the Visual Analog Pain Scale (VAPS: 0-10) in the ENT pediatric department of Trousseau and Necker Enfants Malades Hospitals between 1998 and 2015. PATIENTS All patients had full clinical and electrophysiological checking, and had normal functioning device. Exclusion criteria were: related history of local trauma, ongoing skin infection, magnet displacement, and device failure. INTERVENTION(S) Treatments and outcomes were reviewed, with a minimum of 6 months follow up. Two groups were analyzed: Group PS: pain associated with local swelling (n = 9) and Group P: isolated pain (n = 11). The first-line treatment was medical. In Group PS, anti-inflammatory, pain medication, and antibiotics were used at the same time; in Group P, only anti-inflammatory and pain medication was used. MAIN OUTCOME MEASURE(S) Success was defined when complete resolution of pain and swelling (pain scale = 0). RESULTS Twenty cases out of the 1,448 implanted patients in our department (1.4%) were included. Average age at first occurrence of pain was 15 years (3-22 yr). Mean delay between surgery and pain complaint was 5.8 years (0.25-14). Mean follow up was 2 years (0.5-5 yr).First line medical treatment was successful in eight cases (40%). Of the 12 patients who failed medical treatment and required surgery, two had resolution of pain with magnet change and 10 had resolution with reimplantation. (5/9 patients in Group PS and 7/11 in Group P).Microbiology was performed in 10/20 cases and analysis of explanted devices was performed in 7/10 cases. Positive microbiological culture of soft tissues was positive for 3/10 cases, biofilm was positive for 5/7 cases.Pain in the area of the implanted device can occur shortly after surgery or on long-term follow up. It has been seen in all device types. Pain may be clinically underestimated, as low VAPS grade (

OBJECTIVES To standardize the information for families of children having functional surgery for middle ear malformations, we describe the audiometric results of the subgroup of patients with the most favorable anatomic conditions: viable auditory canal, intact tympanic membrane, mobile stapes, and corresponding to a Jahrsdoerfer score of 8 or higher. STUDY DESIGN Case series, tertiary referral center. METHODS Charts of patients undergoing functional surgery for congenital middle ear malformations were reviewed for demographic data, preoperative Jahrsdoerfer score, ossicular chain status, type of ossiculoplasty, and audiometric data before and 6 months postsurgery. RESULTS Eighteen consecutive interventions were performed on 13 patients (average age of 9 years, 8 girls and 5 boys) between 2004 and 2011. The ossiculoplasties performed were as follows: incus repositioning (4), double-layer tragal cartilage (5), intact native chain reconstruction (3), and partial ossicular prosthesis (6). Mean air bone gap (ABG) was 40.8 ± 12.4 dB preoperatively and 20.9 ± 12.9 dB postoperatively (p < 0.0001). Preoperative and postoperatively mean air conduction PTA thresholds were 49.9 ± 9.5 and 30.0 ± 14.1 dB, respectively (p < 0.0001). All ears operated on except one had air conduction improvement. There were no complications. CONCLUSION Functional surgery for congenital middle ear malformations gives variable hearing outcomes. In this study, with the most favorable anatomic conditions, 12 ears (67%) of 18 had air conduction improvement below 30 dB.

Objective: Unilateral sensorineural hearing loss (USNHL) is known to impact on school performance and social skills during childhood, but the etiologies remain unclear. The aim of this study was to assess various etiologies and to study the clinical contexts in this population. Methods: The study is a retrospective review. Characteristics of hearing loss (HL), audiometric parameters, imaging, and genetic and medical contexts were analyzed. Results: Eighty children were included. USNHL was profound in 68%, could be progressive in 19%, and become bilateral in 7.5% of cases. Inner ear malformations were identified in 41% of cases; cochlear nerve deficiency (CND) was frequent (33%). Cytomegalovirus (CMV) infection and genetic syndromes were confirmed in 10 and 6% of cases, respectively. Conclusion: Long-term hearing follow-up remains useful in USNHL as it can become bilateral. Looking to etiology, MRI should be the gold standard, as CND is frequently observed and screening for CMV infection should be systematic. Genetic etiologies appear to be different compared to bilateral HL. Further genetic research in this domain is needed.

Objective To investigate the implication of SLC26A4, FOXI and KCNJ10 genes in unilateral hearing impairment associated with ipsilateral inner ear malformation (Enlargement of the vestibular aqueduct and/or Mondini dysplasia). Methods We have gathered 25 patients presenting unilateral hearing impairment and ipsilateral enlarged vestibular aqueduct. For each of the patients, we have analyzed SLC26A4, FOXI1 and KCNJ10 genes sequences. Results The analysis of SLC26A4 revealed only eight heterozygous SLC26A4 sequence variants, three of them being novel (p.Met147Ile, p.Asn538Asn and p.Leu627Arg). None of the patients carried a second mutation on the other allele. Moreover, the SLC26A4 locus was excluded by segregation analysis in two families. No mutations were present in FOXI1 and KCNJ10 genes. Conclusions Together, these data suggest that SLC26A4, FOXI1 and KCNJ10 are not major determinants in unilateral deafness and enlarged vestibular aqueduct compared with their implication in Pendred syndrome and non-syndromic bilateral enlarged vestibular aqueduct.

Objective To evaluate the perceptive and linguistic results in 2 predefined genetic population of children with implants. Study design Retrospective cohort study. Setting Otolaryngology department of a tertiary referral hospital. Patients Among 336 children with prelingual deafness who underwent implantation in our department between 1997 and 2007, 85 with GJB2 gene-related (Cx) deafness and 30 patients with Waardenburg syndrome (WaardS) were included. Mean age at implantation was 4.7 years (range, 15 mo to 16.5 yr) in the Cx group and 4.8 years (range, 16 mo to 16 yr) in the WaardS group. The mean follow-up period was 6.5 years (range, 19 mo to 12 yr) in the Cx group and 7.1 years (range, 27 mo to 13.5 yr) in the WaardS group. More than 75% of the families in both groups scored 4 and 5 when using the Mary Pat Moeller rating (p > 0.05). A psychoneurological evaluation was performed in one third of the patients in both groups. Main outcome measures Patients underwent linguistic and perceptive evaluations at 12, 24, 36, and 48 months: speech perception with closed-set and open-set words, speech production (Level 1 = vocalizations to Level 5 = complex sentences), and lexical comprehension with EVIP/GaelP (Peabody Picture Vocabulary Test) tests that ranged in 5 levels (-2 SD to +2 SD). Results Score results for open-set words were 38.5%, 57.5%, 69%, and 75% in the Cx group and 30.5%, 59%, 67.5%, and 78% in the WaardS group (p > 0.05) at 12, 24, 36, and 48 months. The proportion of children in Levels 4 and 5 of speech production was 27%, 42%, 57.5%, and 58% in the Cx group and 23%, 33%, 55%, and 66% in the WaardS group (p > 0.05). Lexical result at Level -2 SD at 1 year was 90% in the Cx group and 85% in the WaardS group and that at 4 years was 70% in the Cx group and 65% in the WaardS group (p > 0.05). Conclusion Perceptive and linguistic evolutions for both populations were of good quality, but lexical evaluation showed residual language difficulties in both groups.

To estimate the prevalence of congenital cytomegalovirus (cCMV) among causes of bilateral hearing loss in young French children.Children3 years old with hearing loss were prospectively included at their first visit to a referral center. Cytomegalovirus polymerase chain reaction was performed on dried blood spots from Guthrie cards. Medical records were reviewed.One hundred children with bilateral hearing loss were included at a median age of 15 months; the prevalence of cCMV was 8% (8/100) (95% CI, 2.7%-13.3%) in this population and 15.4% (8/52) in the subpopulation of children with profound bilateral hearing loss. Delayed neurodevelopment and brain abnormalities on computed tomography scan were found more often in children with cCMV than in children with hearing loss without cCMV (P = .027, P = .005). In 6 of 8 cCMV cases, cCMV infection had not been diagnosed before the study.In a comprehensive study of the causes of bilateral hearing loss in young French children, cCMV is the second most frequent cause of hearing loss after connexin mutations. It underlines that a majority of French children with hearing loss and cCMV are not diagnosed early and therefore may not benefit from early intervention including the possibility of neonatal antiviral treatment. These results make the case for promoting systematic cytomegalovirus screening in neonates with confirmed hearing loss identified through neonatal hearing screening.

Objectives To study children who had undergone stapedectomy at an age younger than 16 years to determine the causes (particularly frequency of congenital anomalies vs otosclerosis) and to analyze the functional results over the short-term, 1-year, and long-term postsurgery time course. Design Ten-year retrospective study covering 1998 to 2008. Setting Pediatric tertiary care centers. Patients A total of 33 patients (35 ears) underwent stapes surgery from October 1998 to October 2008. Main Outcome Measure Sex, age, preoperative and postoperative audiometric test results, associated anomalies, type of surgery (stapedotomy or partial stapedectomy), method of stapes surgery, and complications. Results The median age of patients at surgery was 13.4 years, ranging from 3.3 to 15.9 years. The major cause, which was found in 25 of 35 ears (71%), was nonprogressive conductive hearing loss due to congenital stapes fixation. The second most common cause, which was found in 6 of 35 ears (17%), was otosclerosis with progressive conductive or mixed hearing loss. Three ears presented posttraumatic stapes luxation (1 child aged 3.3 years at surgery). In 1 ear, the cause was osteogenesis imperfecta. Twenty-two ears were treated via the drill or laser-assisted small fenestra technique, and 13 ears were treated by a partial removal of the footplate covered by fascia. Early functional results were good, with a median postoperative air-bone gap of 9.8 dB, and 94% of the results were considered good or very good. There was no significant difference between early, 1-year, and longer-term audiometric results. Conclusions Congenital fixation is the major indication for stapedectomy in children younger than 16 years. Functional results are good and remain stable over time.

Transient deafness associated with an increase in core body temperature is a rare and puzzling disorder. Temperature-dependent deafness has been previously observed in patients suffering from auditory neuropathy. Auditory neuropathy is a clinical entity of sensorineural deafness characterized by absent auditory brainstem response and normal otoacoustic emissions. Mutations in OTOF, which encodes otoferlin, have been previously reported to cause DFNB9, a non-syndromic form of deafness characterized by severe to profound prelingual hearing impairment and auditory neuropathy. Here we report a novel mutation in OTOF gene in a large family affected by temperature-dependent auditory neuropathy. Three siblings aged 10, 9 and 7 years from a consanguineous family were found to be affected by severe or profound hearing impairment that was only present when they were febrile. The non-febrile patients had only mild if any hearing impairment. Electrophysiological tests revealed auditory neuropathy. Mapping with microsatellite markers revealed a compatible linkage in the DFNB9/OTOF region in the family, prompting us to run a molecular analysis of the 48 exons and of the OTOF intron-exon boundaries. This study revealed a novel mutation p.Glu1804del in exon 44 of OTOF. The mutation was found to be homozygous in the three patients and segregated with the hearing impairment within the family. The deletion affects an amino acid that is conserved in mammalian otoferlin sequences and located in the calcium-binding domain C2F of the protein.

Objective To review the presentation and associated congenital abnormalities of laryngeal cleft and present guidelines for its evaluation and management. Design A 10-year retrospective study (1994-2004) with institutional review board approval. Setting Two pediatric tertiary care medical centers. Patients Twenty-two pediatric patients (mean age, 21 months) with laryngeal cleft. Intervention Surgical repair of laryngeal cleft. Main Outcome Measures Sex, age, symptoms, other associated abnormalities, method of evaluation, type of laryngeal cleft, method of surgical repair, treatment outcome, complications, and long-term follow-up. Results All 22 patients underwent surgical repair for laryngeal cleft. Airway endoscopy confirmed the following types of laryngeal clefts: type 1 (n = 3), type 2 (n = 10), and type 3 (n = 9). Surgical repair techniques included an open approach with or without interposition graft (n = 16) and an endoscopic approach (n = 6). Conclusions Early diagnosis and proper repair of laryngeal cleft are essential to prevent pulmonary damage and associated morbidity. Each patient should be assessed properly, and the surgical approach should be individualized based on the symptoms, other associated findings on airway endoscopy, and type of cleft.

Aims: The purpose of the study was to define boundaries between endocochlear hearing loss and auditory neuropathy in children with congenital profound hearing loss and positive otoacoustic emissions. Patient: A child presented with bilateral profound hearing loss, which was confirmed by the absence of evoked auditory potentials at 110 dB and with conserved otoacoustic emissions. The lack of any relevant medical history, a normal neurologic pediatric examination, and the improvement obtained with powerful hearing aids suggested an endocochlear cause. Genetic testing identified mutations in OTOF, responsible for the DFNB9 recessive form of hearing loss. Results: In recent years, cases of children with hearing loss associated with positive otoacoustic emissions have been labeled as “auditory neuropathy.” Classically, this form of hearing loss is refractory to the use of hearing aids and cochlear implants. Mutations in OTOF lead to inner hair cells dysfunction, whereas the outer hair cells are initially functionally preserved. As this form of endocochlear hearing loss can be detected at a molecular level, genetic testing can be proposed for cases of nonsyndromic auditory neuropathy, as those children could benefit from cochlear implantation. Conclusion: It is advisable to reserve the term “auditory neuropathy” for patients who present hearing loss and conserved otoacoustic emissions in the context of a neurologic syndrome or for children with suggestive perinatal history. In other cases, genetic testing for mutations in OTOF should be carried out.

OBJECTIVE To evaluate surgical aspects and results of cochlear implantation in inner ear malformations. STUDY DESIGN Retrospective cohort study. SETTING Ear, nose, and throat department of a tertiary referral hospital. PATIENTS Out of 260 implanted children, 18 (6.9%) had inner ear malformations: complex cochleovestibular malformation (n = 11), common cavity (n = 1), and enlarged vestibular aqueduct (EVA) (n = 6). Deafness was progressive in 12 cases (G1) and congenital in 6 cases (G2). Genetics lead to diagnosis in 12 of 13 cases: PSD mutation (n = 11), Waardenburg syndrome (n = 1), negative (1). Mean age at implant was 7.8 years. Mean follow-up period was 48 months. MAIN OUTCOME MEASURES Medical and surgical outcomes were reported. Closed (CSW) and open (OSW) set word perception and level of speech production were evaluated each year. The results were compared pre- and postoperatively and between the two groups. RESULTS Gusher at surgery was observed in 50% of cases, with a persistent leak in one case. No facial injury or infectious complications were observed. At 12 months, 83% of the population had achieved more than 75% recognition in CSW, versus 16% before implant (p = 0.001). After 2 years, 64% of patients had more than 50% recognition in OSW. Good oral language was seen in 76% at 2 years and 100% at 3 years, versus 55% before implant (respectively, p > 0.05 and p = 0.03). At 1 year after implant, 83% of the G1 and 20% of the G2 achieved more than 50% recognition in OSW (p = 0.02). After 24 months, 83% of G1 and 40% of G2 had more than 50% in OSW (p > 0.05). Before implant, 75% in G1 and 0% in G2 had good oral language (p = 0.01). At 1 year, 83% in G1 and 16% in G2 had good oral language (p = 0.02). At 2 years, 100% in G1 and 20% in G2 had good oral language (p = 0.02). One child in G1 had no improvement after implantation. CONCLUSIONS No major complication was seen. Perceptive and linguistic results were variable and depended on the type of the deafness. In progressive deafness, the perceptive and linguistic result are expected to be good. In congenital deafness, the results are more variable.

ObjectiveThe nasal dermoid sinus cyst (NDSC) is an uncommon congenital lesion presenting as a large panel of midline craniofacial anomalies. The objective of this study was to review and reanalyze embryological hypotheses concerning NDSCs and to propose an embryological theory unifying the various anatomical characteristics of these lesions. The first case of frontal localization of a NDSC extending within the diploetic bone in a 9-month-old boy, presenting as a median frontal fistula with recurrent frontal swelling, 6 months after a mild frontal trauma is presented.ResultsComplete surgical removal was performed, and there was no evidence of either persistent or recurrent disease 2 years after his surgery. The embryological and anatomical origins of NDSCs are reviewed. This article reexamines and discusses major embryological theories on NDSC pathogenesis and proposes to refute the “prenasal space” theory of Grünwald and rehabilitate a forgotten embryological hypothesis, which unifies the main various clinical presentations of NDSCs.

ObjectivesCongenital sinuses or fistulas of the lip are uncommon malformations, yet true medial upper-lip fistulas (MULFs) are extremely rare. We present a new case of congenital upper-lip fistula located in the midline of the philtrum of an 8-month-old girl.InterventionComplete surgical removal was performed with a combined extra- and intraoral approach. Histological examination revealed that the fistula was lined by squamous epithelium with sebaceous and mucous glands and hair follicles.ResultsSeveral embryological hypotheses have been proposed concerning these anomalies. This article reexamines and discusses major embryological theories on pathogenesis of sinuses or fistulas of the upper lip. We propose that early ectodermal inclusion events may occur in the medial fusion area during formation of the intermaxillary process. This embryological approach is highly concordant with our recent hypothesis on nasal dermoid sinus cysts (NDSCs) pathogenesis, in which we proposed an embryological hypothesis with early ectodermal inclusion phenomenon in the midline suture area to explain NDSCs pathogenesis.ConclusionsCommon early ectodermal inclusion phenomena could be involved in both NDSCs and MULFs pathogenesis.

Objective : To describe a rare complication of cochlear implantation such an osteoma on the magnet. Study design : Retrospective case review. Setting : ENT Department of otolaryngology, Armand Trousseau Pediatrics Hospital, Paris, France. Patients : A four year old child presenting a pain and a redness at the site of implantation of the magnet after a minor head injury. He was implanted two years before with a Nucleus 24 device at the age of 18months. Intervention : Surgery was limited to the revision of the site receiver/stimulator and excision of the osteoma. Results : Postoperative audiogram and clinical monitoring. Conclusion : First case of osteoma described at the magnet of a cochlear implant in a minor head trauma.

Objective To evaluate the results of velopharyngoplasty for velopharyngeal insufficiency (VPI) in relation to 22q11 deletion or nonsyndromic VPI. Design Retrospective study. Setting Academic medical center. Patients Eleven of 45 patients with 22q11 microdeletion (group 1) and 9 patients without 22q11 microdeletion (group 2) with noncleft VPI (hypoplastic velum or hypodynamic velopharynx and deep pharynx) underwent velopharyngoplasty (midline pharyngeal flap with superior pedicle). Exclusion criteria included cleft palate, submucous cleft palate, all syndromic cases, and all associated malformations (except those related to 22q11 microdeletion in patients with DiGeorge syndrome). Main Outcome Measures Speech assessment before surgery using the Borel-Maisonny scale and at 9 months and 24 months after surgery. Velopharyngeal insufficiency was classified as normal, inconsistent, mild, moderate, and severe. Results Before surgery, in group 1, 3 patients had mild and 8 had severe VPI, and in group 2, 1 had mild and 8 had severe VPI. Postoperative outcomes at 9 months showed that in group 1, 2 patients had excellent results (normal and inconsistent) and 9 had mild VPI, while in group 2, 6 patients had excellent results and 3 had mild VPI ( P = .03). Postoperative outcomes at 24 months showed that in group 1, 10 patients had excellent results and 1 had mild VPI, while in group 2, 8 patients had excellent results and 1 had mild VPI. Conclusions Surgical treatment of noncleft VPI by pharyngoplasty was efficient in 10 of the 11 patients (91%) in the 22q11 group and in 8 of the 9 patients (89%) in the nonsyndromic group. Postoperative remission took longer for patients with the 22q11 microdeletion than for the control group. However, long-term results following surgical treatment were equally good in the 2 groups.

Magnet displacement is a rare but possible complication in patients with cochlear implants. We report 1 case in a young child that occurred during magnetic resonance imaging scanning, despite precautionary measures taken by the surgeon and the radiographer.Retrospective case report.This case is presented by the ENT Department of Armand Trousseau Paediatrics Hospital, Paris, France.An 8-year-old child, implanted with a Freedom Contour Nucleus cochlear implant, was referred for a 1.5-T cerebral magnetic resonance imaging because of a progressive neurologic disorder.This rare complication underlines the importance of risk information and preventive measures required, even in case of compatible devices, for performing a magnetic resonance imaging examination in patients wearing a cochlear implant with removable magnet.

Objectives To analyze the clinical features of hearing impairment and to search for correlations with the genotype in patients with DFNB1. Design Case series. Setting Collaborative study in referral centers, institutional practice. Patients A total of 256 hearing-impaired patients selected on the basis of the presence of biallelic mutations in GJB2 or the association of 1 GJB2 mutation with the GJB6 deletion ( GJB6 -D13S1830)del. Main Outcome Measures The prevalence of GJB2 mutations and the GJB6 deletion and audiometric phenotypes related to the most frequent genotypes. Results Twenty-nine different GJB2 mutations were identified. Allelic frequency of 35delG was 69%, and the other common mutations, 313del14, E47X, Q57X, and L90P, accounted for 2.6% to 2.9% of the variants. Concerning GJB6 , ( GJB6 -D13S1830)del accounted for 5% of all mutated alleles and was observed in 25 of 93 compound heterozygous patients. Three novel GJB2 mutations, 355del9, V95M, and 573delCA, were identified. Hearing impairment was frequently less severe in compound heterozygotes 35delG/L90P and 35delG/N206S than in 35delG homozygotes. Moderate or mild hearing impairment was more frequent in patients with 1 or 2 noninactivating mutations than in patients with 2 inactivating mutations. Of 93 patients, hearing loss was stable in 73, progressive in 21, and fluctuant in 2. Progressive hearing loss was more frequent in patients with 1 or 2 noninactivating mutations than in those with 2 inactivating mutations. In 49 families, hearing loss was compared between siblings with similar genotypes, and variability in terms of severity was found in 18 families (37%). Conclusion Genotype may affect deafness severity, but environmental and other genetic factors may also modulate the severity and evolution of GJB2-GJB6 deafness.