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Biomedical subjects

F Denoyelle

Publications and source records attributed to F Denoyelle.

At least 19 recordsLinked to original sources
PubMed2001

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.

Adult↗
PubMed2001

[Episodic laryngeal dysfunction].

Episodic laryngeal dysfunction (ELD), also known as paradoxical vocal cord dysfunction or laryngeal dyskinesia, is characterized by abnormal closure of the vocal cords during inspiration (and sometimes at the very start of expiration). It can manifest in different ways depending on the patient's age. In the newborn, it is usually associated with stridor restricted to the inspiratory breath following crying, and the natural history is always one of rapid resolution. Occasionally, a more severe form presents with intense dyspnea and marked inspiratory stridor in a baby that usually has extensive gastroesophageal reflux which has not been treated adequately enough to improve the dyspnea or the associated vasovagal attacks. A tracheotomy may be necessary. It is rare for this disease to present between the ages of 2 and 8 years. Thereafter, it may present as a form of pseudo asthma resistant to bronchodilators and anti-inflammatory drugs. The dyspnea can be very severe and lead the family to seek hospital admission, at least during the initial episodes. There is a female preponderance. The key to making the diagnosis is the complete reversibility of the patient's symptoms when they are distracted. Exertion asthma can be mimicked by forms of ELD that occur only by effort (apart from the profile of the lung function tests). There may be significant gastroesophageal reflux. Medical intervention (hospitalization and tracheotomy) must be avoided, treatment being essentially behavioral. Finally, some cases of paradoxical adduction of the vocal cords have been described with the use of neuroleptics, brain stem compression, cortical lesions and, much more rarely, motoneuron disease. This diagnosis requires a high index of suspicion, particularly in patients with asthma whose presentation or clinical course with treatment is atypical.

Age Factors↗
PubMed2000

[Hereditary sensorineural deafness].

Deafness is the most common sensory defect. The investigation of the cause of deafness is critical for genetic counselling, and sometimes for appropriate management of associated pathologies. About two thirds of cases of congenital deafness are genetic forms, and the proportion is probably similar concerning the forms of deafness that appears during childhood. Some of the genetic forms are syndromic and the associated signs are sometimes inapparent or may appear during childhood. Consequently, a systematic search for the most frequent syndromes is necessary in each deaf individual. In the majority of genetic cases, deafness is the sole defect (non-syndromic deafness) and the major mode of transmission is autosomal recessive. The DFNB1 form of deafness, due to connexin 26 gene mutations, underlies half of the cases of non syndromic congenital deafness cases. The hearing loss has a prelingual onset, and it is most frequently severe or profound. There is no associated pathologies or radiological anomalies of the inner ear, and the vestibular tests are normal. The possibility of offering molecular diagnosis of connexin 26 gene defects is profoundly modifying daily medical practice in the investigation of the cause of deafness.

Connexin 26↗
PubMed2000

Extensive lymphangioma presenting with upper airway obstruction.

OBJECTIVE: To describe the results of an outcome survey of 18 cases of pediatric lymphangioma with dyspnea from encroachment on the tongue base, parapharyngeal space, and/or larynx. DESIGN: Retrospective review of files from January 1983 to September 1998. SETTING: Pediatric otolaryngology departments from 2 referral centers. PATIENTS: Eighteen patients were treated. The average age at initial surgery was 22 weeks (median, 5 weeks). All presented with at least unilateral suprahyoid and infrahyoid cavernous (microcystic) lymphangioma. The tongue base was involved in 11 patients, the parapharyngeal space in 12, and the larynx in 8. INTERVENTIONS: Neck dissection was performed initially in all patients. Tracheotomy was performed in 9 patients (50%). Macroglossia was treated by V glossoplasty. Parapharyngeal extensions were treated by cervicotomy or endoscopy, and larynx and tongue base extensions by carbon dioxide laser photocoagulation. Supraglottic laryngectomy was performed in 2 patients. MAIN OUTCOME MEASURES: Residual disease, decannulation, duration of tracheotomy, and persistent respiratory symptoms. RESULTS: The average follow-up was 4 years postoperatively. One postoperative death occurred. Sixteen (94%) of the remaining 17 patients had residual lymphangioma. Eight (89%) of the 9 patients with tracheotomy underwent decannulation (average duration, 22 months). Ten patients had persistent symptoms, and 6 were asymptomatic. CONCLUSIONS: Involvement of the upper airway seems to be the determining prognostic factor in extensive lymphangioma. Patients with dyspnea by external compression of cervical lymphangioma on the airway responded well to surgery. Aggressive surgical treatment did not seem to significantly improve the prognosis in patients with intrinsic involvement of the upper airway. The natural evolution of untreated massive lymphangioma has not been documented. Less aggressive, symptomatic therapy may be an alternative to avoid mutilating surgery in patients with intrinsic involvement of the airway.

Airway Obstruction↗
PubMed2000

A simple and reliable method for the detection of the 30delG mutation of the CX26 gene.

Mutations in the CX26 gene (GJB2), encoding the gap-junction protein Connexin-26, have been shown to be the major cause of non-syndromic recessive deafness. Among these mutations, the deletion of a guanine within the stretch of six G between nucleotide positions +30 and +35 of the CX26 cDNA (30delG) accounts for the majority of this kind of deafness. Molecular detection of the 30delG mutation is usually performed by direct sequencing analysis of PCR products or by SSCP. To detect this mutation we developed an easy and reliable method, based on PCR, followed by a non-radioactive sandwich hybridization on microtiter plates. We tested 188 individuals recruited from the genetic counseling service for deaf people at the Pasteur Hospital and at the Armand-Trousseau Children's Hospital, Paris, France between April 1997 and September 1998. Our screening method is simple, uses stable and safe reagents, and employs inexpensive equipment. As such, it is suitable for widespread use in genetic diagnosis.

Connexin 26↗
PubMed2000

Use of the carbon dioxide laser for tracheobronchial pathology in children.

The carbon dioxide (CO2) laser has been used to treat tracheobronchial pathology for more than 20 years. It was initially employed in adults and now has been found to be useful in the treatment of certain lesions in children. We present our experience with this technique in 30 patients treated with a CO2 bronchoscopic laser from 1987 to 1995 in the Ear, Nose, and Throat Department of Armand Trousseau Hospital. Four different types of pathologies have been successfully treated with the laser: selective cases of tracheobronchial stenosis following trauma and/or secondary to neonatal ventilation, posttraumatic tracheobronchial granuloma (due to foreign bodies or tracheotomies), tracheobronchial granulomas of infectious origin (tuberculosis), and selective cases of tracheobronchial tumor.

Adolescent↗
PubMed2000

Mutations of GJB2 in three geographic isolates from northern Tunisia: evidence for genetic heterogeneity within isolates.

Geographically isolated populations have been successfully used to localize genes for recessive inherited diseases, including non-syndromic sensorineural recessive deafness (NSRD). To date, 25 loci for NSRD have been localized on human chromosomes (DFNB loci), and six of the corresponding genes have been identified. Here, we report on the contribution of the DFNB1 locus (GJB2 gene) to NRSD in seven affected families living in three northern Tunisian geographic isolates, and we provide evidence for genetic heterogeneity within isolates. This finding challenges the classical view of a single 'founder' mutation segregating in such isolates.

Alleles↗
PubMed2000

DFNA3.

Explore the source record for details and available documents.

Chromosome Mapping↗
PubMed1999

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.

Case-Control Studies↗
PubMed1999

Townes-Brocks syndrome: detection of a SALL1 mutation hot spot and evidence for a position effect in one patient.

Townes-Brocks syndrome (TBS) is an autosomal dominant developmental disorder characterized by anal and thumb malformations and by ear anomalies that can affect the three compartments and usually lead to hearing loss. The gene underlying TBS, SALL1, is a human homolog of the Drosophila spalt gene which encodes a transcription factor. A search for SALL1 mutations undertaken in 11 unrelated affected individuals (five familial and six sporadic cases) led to the detection of mutations in nine of them. One nonsense and six different novel frameshift mutations, all located in the second exon, were identified. Together with the previously reported mutations [Kohlhase et al., 1999], they establish that TBS results from haploinsufficiency. The finding of de novo mutations in the sporadic cases is consistent with the proposed complete penetrance of the disease. Moreover, the occurrence of the same 826C>T transition in a CG dimer, in three sporadic cases from the present series and three sporadic cases from the other series [Kohlhase et al., 1999] (i.e., six of the eight mutations identified in sporadic cases), reveals the existence of a mutation hotspot. Six different SALL1 polymorphisms were identified in the course of the present study, three of which are clustered in a particular region of the gene that encodes a stretch of serine residues. Finally, the chromosome 16 breakpoint of a t(5;16)(p15.3;q12.1) translocation carried by a TBS-affected individual was mapped at least 180 kb telomeric to SALL1, thus indicating that a position effect underlies the disease in this individual.

Abnormalities, Multiple↗
PubMed1999

Myringoplasty in children: predictive factors of outcome.

OBJECTIVES: To assess the results of myringoplasty in children and to determine which factors independently influence the postoperative results. STUDY DESIGN: Retrospective study of the anatomic and functional results of 231 consecutive myringoplasties performed in 188 children between 1988 and 1992. Multivariate analysis of poor prognostic factors by cross-sectional comparison 1 year after surgery. METHODS: Myringoplasties were performed via an endaural approach with a fascia temporalis underlay graft. RESULTS: In 216 of 231 ears (93.5%) the tympanic membrane was closed. A good anatomic outcome was considered to have been achieved in 188 ears (81.6%), although in 18 ears (7.8%) seromucous otitis media occurred, in 8 ears (3.5%) a progressive retraction pocket was encountered, and in 2 ears significant lateralization was present. One hundred thirty-nine (67.5%) of the 206 ears tested in the postoperative period had a postoperative air-bone gap of 10 dB or less. On average, mean bone conduction remained unaltered. The age of the patient and the size and the location of the perforation did not affect the outcome. Three prognostic factors for an abnormal postoperative tympanic membrane were found, with 95% confidence intervals: inflammatory changes in the middle ear mucosa (P < .05), contralateral tympanic perforation (P < .05), and contralateral cholesteatoma (P < .01). CONCLUSIONS: Myringoplasty with underlay grafting of the fascia temporalis in children gives good anatomic and functional results. Inflammatory changes within the middle ear mucosa, contralateral tympanic perforation, and contralateral cholesteatoma independently influence the risk of an abnormal postoperative tympanic membrane. The presence of one of these factors preoperatively should lead to the consideration of alternative, more durable graft material, such as autologous cartilage.

Adolescent↗
PubMed1998

A particular case of deafness-oligodontia syndrome.

Two previous case reports described two sibs affected with both sensorineural hearing loss and oligodontia. Here, we report a similar syndrome in a male patient with an, as yet, undescribed vestibular aqueduct enlargement on tomodensitometry. The analysis of the parent's audiograms is consistent with the suggested autosomal recessive mode of inheritance of this disorder.

Anodontia↗
PubMed1998

Results of tympanoplasty in children with primary ciliary dyskinesia.

OBJECTIVE: To assess the results of tympanoplasty in children with primary ciliary dyskinesia complicated by tympanic perforation or cholesteatoma with hearing loss and/or recurrent otorrhea. DESIGN: Retrospective study. Postoperative follow-up of 26.3 months in the type 1 tympanoplasty group and 46 months in the child with cholesteatoma. SETTING: Hospitalized care, referral center. PATIENTS: Seven children with primary ciliary dyskinesia, complicated in 6 children by 9 tympanic perforations (3 bilateral perforations) and in 1 child by an attical cholesteatoma. RESULTS: After 9 type 1 tympanoplasties, the grafts were intact in 9 ears, with no recurrence of otorrhea, but serous otitis media was present in 6 of the 9 ears. Auditory improvement was significant, with an average gain of 17-dB hearing level in speech frequencies. After a canal wall-down tympanoplasty with mastoidectomy for attic cholesteatoma in 1 ear, the cavity that was operated on showed no signs of otorrhea or residual cholesteatoma after a follow-up of 46 months. CONCLUSION: In children with primary ciliary dyskinesia, tympanoplasty has a high probability of graft success and auditory improvement, despite the frequent recurrence of serous otitis media.

Adolescent↗
PubMed1998

Posterior laryngeal clefts: preliminary report of a new surgical procedure using tibial periosteum as an interposition graft.

OBJECTIVE: To present the preliminary results of a new surgical procedure for posterior laryngeal cleft repair. DESIGN: Retrospective study in an academic tertiary care center. METHOD: The study included three male patients (age at surgery, 2, 13, and 14 mo). One presented with severe aspiration and cyanotic attacks, the two others with aspiration and recurrent chest infections. The types of laryngeal clefts included complete cleft of the cricoid with varying degrees of tracheal involvement but not further than the first six tracheal rings. Associated malformations included one VATER syndrome, one esophageal atresia, and one tracheoesophageal fistula. Surgery was performed under general anesthesia with nasotracheal intubation. A vertical anterior laryngofissure was performed. The mucosal margins of the clefts were incised and then repaired in two layers with polyglactin sutures. The original feature of this procedure was the interposition of a small piece of tibial periosteum between the two layers. This fascia graft is known to be strong and resistant in cleft palate surgery. MAIN OUTCOME MEASURE: Clinical and endoscopic follow-up was used for evaluation of results. RESULTS: The three patients had successful laryngeal repair at a mean follow-up of 6 months (range, 4-14 mo). CONCLUSION: The anterior laryngofissure provides a good surgical access to the cleft. The interposition of tibial periosteum allows durability of the cleft repair. A longer follow-up is needed to confirm these preliminary results. A computed tomography scan study and a study on the rabbit are planned in order to evaluate the outcome of these periosteal grafts.

Adolescent↗
PubMed1998

[Etiological diagnosis of sensorineural deafness in children: a year-long review of genetic counseling for deaf people].

From February 1996 to January 1997, 74 patients from 53 sibships underwent genetic counselling for sensorineural deafness at the Pasteur Hospital, Paris, France. Genetic counselling was based on the etiological diagnosis of the hearing impairment, by an audiological and non-audiological examination program. At the first examination, 31 families presented with a familial deafness and 22 families with apparently one affected individual. However, familial audiological examinations revealed familial deafness in 5 of these 22 families. Consequently, a total of 36 families had hereditary hearing impairment and the etiological groups showed the following distribution: non-syndromic deafness (14 families), syndromic deafness (12 families), probable syndromic deafness (5 families), and incomplete assessment (5 families). Out of the remaining 17 families in which affected individuals were sporadic cases, the etiological groups were as follows: acquired deafness (2 families), probable syndromic deafness (5 families), unknown cause (5 families), and incomplete assessment (5 families). Etiological assessment is discussed, with reference to the cost-effectiveness of this examination program. In light of this preliminary report, we present a model of assessment for the etiological diagnosis of sensorineural deafness in children and young adults.

Adolescent↗
PubMed1997

Discoordinate pharyngolaryngomalacia.

In cases of severe laryngomalacia, laser division of the aryepiglottic folds (AEFs) or endoscopic supraglottoplasty may be an ineffective solution. Failure of this technique is rare and the reasons for failure are not well established. The purpose of this study was to describe those cases of laryngomalacia in which endoscopic treatment did not reverse the clinical situation. We introduce the concept of discoordinate pharyngolaryngomalacia (DPLM). DPLM was defined as severe laryngomalacia with complete supraglottic collapse during inspiration, without shortened AEFs or redundant mucosa, and with associated pharyngomalacia. Twenty-seven of 82 children with severe laryngomalacia presented a DPLM. Endoscopic treatment was performed in 16 children and the surgical procedure was inadequate to reverse the clinical problem in these patients. In 10 children correction of additional sites of obstruction was required (uvulopharyngopalatoplasty, surgery of choanal atresia, aortopexy). Tracheostomy was necessary in 13 children. Bi-level positive airway pressure (BiPAP) was used successfully in 2 children and tracheotomy was avoided. Treatment still needs to be better defined.

Endoscopy↗