Primary ovarian insufficiency in RMND1 mitochondrial disease.

RMND1 (Required for Meiotic Nuclear Division 1 homolog) is a nuclear encoded mitochondrial protein. Biallelic variants inRMND1are described in patients with white matter encephalopathy, hearing loss and renal dysfunction. In addition to this phenotype, two independent families (3 patients) have been reported with ovarian failure. We report on a 17-year-old girl with RMND1 related mitochondrial disorder including white matter encephalopathy, hearing loss and renal insufficiency who presented primary ovarian insufficiency in whom a homozygous variant c.713 A > G (p.Asn238Ser) in the RMND1 gene was found. We report the fourth patient with RMND1 biallelic pathogenic variants and primary ovarian insufficiency.

COVID-19 and ENT Pediatric otolaryngology during the COVID-19 pandemic. Guidelines of the French Association of Pediatric Otorhinolaryngology (AFOP) and French Society of Otorhinolaryngology (SFORL).

OBJECTIVE: Joint guidelines of the French Pediatric Otolaryngology Society (AFOP) and of the French Society of otorhinolaryngology-head and neck surgery (SFORL) on the management of paediatric otolaryngology patients in the context of the COVID-19 pandemic. METHODS: A nation-wide workgroup drew guidelines based on clinical experience, national and local recommendations and scientific literature. Proposals may have to be updated on a day-to-day basis. RESULTS: In children, incidence of symptomatic COVID-19 (1-5%) is low and of good prognosis. The indications for nasal flexible endoscopy should be drastically limited. If undertaken, full Personal Protective Equipment (PPE) including FFP2 masks are required, as well as use of a sheath. Saline nose wash done by caregivers other than parents at home should require PPE. Unless foreign body tracheobronchial aspiration is clinically obvious, CT-scan should be performed to confirm indication of endoscopy. Surgical indications should be limited to emergencies and to cases that cannot be delayed beyond 2 months (especially endonasal, endopharyngeal laryngo-tracheobronchial procedures). Postponement should ideally be a group decision and recorded as such in the medical file. Surgical techniques should be adapted to limit the risk of viral dissemination in the air, avoiding the use of drills, microdebriders, monopolar cautery or lasers. Continuous suction should be placed near the operating field. In case of confirmed Covid-19 cases, or suspected cases (or in some centres systematically), PPE with FFP2 mask should be worn by all staff members present in the operating room.

Olfactory stimulation may promote oral feeding in immature newborn: a randomized controlled trial.

Premature newborns have an increased mortality and morbidity due to respiratory immaturity and inefficient oral feeding performance. Transient assistance with feeding tubes until oral performance improves is required with consequent hospital admission. Based on a controlled and randomized study, we tested whether olfactory stimulation compared to odorless stimulation could accelerate the switch from feeding tube to satisfactory oral feeding. Fifty newborns were included and randomly assigned to either odorless or olfactory stimulation with anise or cinnamon. The main outcome measurement was the duration of the hospital stay. The odor-stimulated group could be discharged from hospital on average 3.4 days earlier than the control group (p = 0.12). When including only more mature newborns into the analysis (n = 39), the difference was statistically significant (p < 0.05). This trend emphasizes that olfaction may have its place in early feeding stimulation.

Interest of vestibular evaluation in sequentially implanted children: Preliminary results.

INTRODUCTION: An early acquired or congenital absence of sensory input of the vestibule will lead to severe delayed posturomotor milestones. Previous studies have proven modifications and even complete ipsilateral loss of vestibular function after unilateral cochlear implantation. The objective of this study was to evaluate whether sequential cochlear implantation has an impact on vestibular function. METHODS: Retrospective study from January 2012 to January 2015 including 26 patients. The first stage consisted of determining the vestibular status of 26 hearing impaired children who were candidates for a second cochlear implant. Three months after contralateral implantation, we reevaluated the vestibular function of the same patients. The vestibular evaluation consisted of multiple tests for canal and otolith function. A complete clinical vestibular evaluation was performed, including the head thrust test. This was followed by an instrumental assessment composed of the classic bicaloric test and vestibular evoked myogenic potentials testing with tone bursts. RESULTS: A high prevalence of vestibular dysfunction (69%) was found in our group of unilaterally implanted children. Three patients had a unique functional vestibule at the not yet implanted ear. Vestibular evoked myogenic potentials responses stayed present in 15 of the 19 patients with a VEMP-response before contralateral implantation. Results of the caloric test changed for 6 patients after contralateral implantation. CONCLUSIONS: After contralateral implantation, 37% of our patients manifested modifications of their vestibular status. Intrasubject comparison of bicaloric and vestibular evoked myogenic potentials testing before and after contralateral cochlear implantation showed that canal function was better preserved than saccular function. Seeing the high prevalence of vestibular dysfunction in our test group of unilateral implanted children, sequential implantation must be preceded by a vestibular assessment to prevent complete bilateral vestibular areflexia and its potential consequences. Presence of hyporeflexia at the yet-to-be implanted ear seems to be a situation particularly at risk.

[Newborn screening : the point of view of the paediatrician]. / Dépistage néonatal : le point de vue du pédiatre.

Newborn screening is a public health effort that has changed the prognosis of some congenital diseases. Newborn screening programmes differ between countries in which it is organized. Demographic, epidemiological or economic factors play a role in the choice of the screening panel. In the French Community of Belgium, the programme focuses on 13 metabolic and endocrine diseases, hearing loss and hemoglobinopathies (Brussels and Liege). Newborn screening is a complex process that requires the involvement of all stakeholders : parent information, blood sampling or testing, lab analysis, follow-up of the results, initiate adequate care in case of positive test and genetic counselling. Newborn screening programmes will evolve in the next years. New therapeutic and diagnostic methods will make other genetic diseases candidates for screening. Whole genome sequencing may be the next expansion; it will create new opportunities but will pose new ethical dilemmas. We must all prepare now for future challenges.

Hearing loss is part of the clinical picture of ENPP1 loss of function mutation.

BACKGROUND: Ecto/nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) loss-of-function mutations have been described in patients with autosomal recessive hypophosphatemic rickets (HR), in patients with generalized arterial calcification of infancy (GACI) and in several patients with both conditions. Out of more than 50 cases of homozygous or compound heterozygous ENPP1 loss-of-function mutations published so far, 1 case with labyrinthine deafness probably due to occlusion of inner ear supplying arteries and 2 cases of conductive hearing loss due to stapedovestibular calcification diagnosed in childhood have been reported. AIMS: To report a case of ENPP1 loss-of-function novel mutation presenting with HR and very early onset and severe hearing loss. METHODS: Case report and review of the literature. RESULTS: We report on a patient homozygous for a novel 1-bp deletion in ENPP1 that presented with GACI evolving towards HR associated with a mixed hearing loss (both labyrinthine and conductive) diagnosed at 9 days of life that evolved towards profound labyrinthine deafness. CONCLUSION: Hearing loss is a rare finding in patients with ENPP1 loss-of-function mutations. Interestingly, it has already been described in other affected patients, in ENPP1 knock-out mice and in other diseases of pyrophosphate metabolism. Conversely it seems to be absent in children with the X-linked form of HR.

Clinical aspects of chronic ENT inflammation in children.

In children, all ENT cavities are particularly prone to the development of chronic inflammation. This is due to many predisposing factors, of which the most common are unfavourable anatomy, absence of nasal blowing, day care attendance, allergy, immature immunity, gastro-oesophageal reflux and tobacco smoke exposure. The aim of this paper is to outline the most specific paediatric clinical aspects of chronic pharyngo-tonsillitis, rhinosinusitis, otitis media, adenoiditis and laryngotracheitis and the important influence that some of these pathologies exert on the others.

Necrotic adenoids in post-transplant lymphoproliferative disorders.

PROBLEM: Post-transplant lymphoproliferative disorders (PTLD) are a potentially fatal complication after solid organ transplantation. The majority of cases are associated with Epstein Barr virus infection (EBV). The first manifestations of PTLD are frequently observed in the ENT area with adenoidal and/or tonsillar enlargement. METHODOLOGY: We present the case of a 12-year old girl with a total nasal obstruction and tonsillitis five months after a kidney transplantation for bilateral congenital kidney hypoplasia. RESULTS: The EBV genome was detected by polymerase reaction three months after surgery. Fiberoptic examination revealed an obstructive necrotic mass in the naso-pharynx. The anatomic-pathologic analysis revealed necrotic adenoids. CONCLUSIONS: Necrotic tonsillitis is common. Necrosis of the adenoids, although rarer, can also occur and explains the important respiratory distress. Since two thirds of PTLD patients present with clinical symptoms in the ENT area, the otorhinolaryngologist should be aware of this complication.

Familial CHARGE syndrome because of CHD7 mutation: clinical intra- and interfamilial variability.

CHARGE syndrome (OMIM #214800) is a multiple malformation syndrome with distinctive diagnostic criteria, usually because of CHD7 (chromodomain helicase DNA binding 7) haploinsufficiency. Familial occurrence of CHARGE syndrome is rare. We report six patients from two Caucasian families (both with one parent and two children) affected by mild to severe CHARGE syndrome. Direct sequencing of the CHD7 gene was performed in these two unrelated families. A mutation in exon 8 (c.2501C>T - p.S834F) in first chromodomain was found in family A and a nonsense mutation in exon 2 (c.469C>T - p.R157X) in family B. Both mutations are de novo in the parents. In family A, the elder son had bilateral cleft lip and palate, esophageal atresia with fistula, complex heart defect and vertebral abnormalities, while the younger had a posterior coloboma. Their mother had asymptomatic vestibular dysfunction and retinal coloboma, identified after the molecular diagnosis of her children. In family B, both affected children had severe expression of CHARGE syndrome. The father carrying the mutation only had asymmetric anomaly of the pinnae. These familial reports describe the intrafamilial variability of CHARGE syndrome, and underline the presence of CHD7 mutations in patients who do not fit the 'classical clinical criteria' for CHARGE syndrome.

Clinical findings and PDS mutations in 15 patients with hearing loss and dilatation of the vestibular aqueduct.

Following systematic skull imaging of hundred and sixty seven individuals attending a medical referral centre for the deaf in Brussels, Belgium, fifteen patients (9 per cent) aged between two and 25 years were diagnosed with dilatation of the vestibular aqueduct. Careful audiological study, with a baseline assessment then longitudinal follow up, indicated mild to profound deafness with a progressive course (i.e. an average loss of 3.3 dB per year) and frequent dizziness. Sequencing of PDS was performed in all individuals. Alterations of this gene (either homozygous, heterozygous or compound heterozygous base changes) were found in 53 per cent of patients with a large vestibular aqueduct. Four new mutations (two missense, a splice site and a four base pair insertion) were described. We were unable to confirm a correlation between homozygosity, heterozygosity and a Pendred or deafness-only phenotype.

[Deafness in children]. / La surdité de l'enfant.

Considerable progress has been achieved these last years in the field of hearing screening, diagnosis of hearing loss in children and rehabilitation methods. It is now generally accepted that every child with hearing impairment must receive intervention before six months of age. This is only possible thanks to early and systematic hearing screening. The objective screening methods--transient evoked otoacoustic emissions and automated auditory brainstem responses--have excellent specificity and sensitivity and are non invasive. They have replaced the subjective techniques which resulted in a high percentage of false negative cases. The performance of etiologic assessments has dramatically improved, thanks to advancements in genetics and imagery. The identification of deafness-causing genes has provided an insight into inner ear physiology and has permitted to clarify a great number of recessive deafness cases. Computed tomographic and magnetic resonance imaging allow much more precise information gathering about the integrity of the auditory pathway. Finally, cochlear implantation has deeply modified the social and educational prognosis of the severe or profound deaf child. In the vast majority of cases, children implanted early and who do not present associated handicaps, will succeed in communicating within the hearing world and will attend mainstream schools.

Apertura pyriformis stenosis in the newborn.

Apertura pyriformis stenosis in the newborn. Respiratory distress in the newborn can have a variety of aetiologies, the best known of which are cardiac and pulmonary diseases. Major nasal airway obstruction is probably often overlooked when acute desaturation of the neonate requires reanimation procedures, although it is well established that the baby is an obligate nose breather at birth. Nasal airway stenosis or atresia could account for a number of unexplained deaths in the delivery room. In the differential diagnosis of major nasal airway obstruction in the newborn, choanal atresia is by far the most common aetiology. However, a few cases of pyriform aperture stenosis have been reported. One child presenting this pathology was recently treated at the Brussels University Children's Hospital. Unexpectedly, the baby survived until 3 months without any medical support but had severe feeding problems. The diagnosis was confirmed by naso-sinusal CT scan. Surgery was performed at 4 months through an unusual endonasal approach which seems to be less traumatic than the classical sublabial approach. The post-operative course was satisfactory. The 9-month-old patient does not now show residual breathing problems. The presentation will focus on this unusual case.

Long-term follow-up of UCLP at the Reine Fabiola Children's Hospital.

BACKGROUND: The purpose of this retrospective of prospectively acquired data was to evaluate and to compare global evolution in children with complete unilateral cleft lip and palate treated at the Brussels cleft centre following two different surgical treatment protocols. METHODS: A series of forty-four patients operated for non-syndromic complete unilateral cleft lip and palate were included in this study at the age of approximately ten years. Twenty-six children (17 males, 9 females) were treated according to the Malek surgical treatment protocol: the soft palate was closed at a mean age of 3 months, followed by simultaneous repair of the lip and hard palate at a mean age of 6 months. Eighteen children (15 males, 3 females) underwent one-stage "all-in-one" closure of the lip, hard and soft palate at a mean age of 3 months. Craniofacial morphology was evaluated by means of digital lateral cephalometric analysis. Cephalometric data were compared to a control, non-cleft group (n = 40) matched according to age. Data concerning otological status and speech were collected in the same series of children. RESULTS: Statistical analysis showed that the inclination of the maxillary (MxPVSN) plane to the anterior cranial base was significantly increased (p <0.001) in both cleft groups compared to the non-cleft group and significantly increased (p = 0.002) in the Malek cleft group compared to the "all-in-one" cleft group. Otological status was not improved by an early complete closure but by close follow-up and the repeated placement of ventilating tubes. Speech was found to be satisfactory in the majority of children of both groups at six years after speech therapy. Only 15% needed further surgery with pharyngeal flaps. CONCLUSIONS: There were no significant differences in anteroposterior midfacial morphology between the Malek and "all-in-one" protocols at ten years of age. One-stage "all-in-one" closure resulted in less downward inclination of the maxillary plane to the anterior cranial base compared to the Malek protocol at ten years of age. Early complete closure of the cleft resulted in no significant change in otological status or the occurrence of nasality. However, early complete closure of the cleft allowed for earlier intelligibility of speech compared to the staged later closure.

Petrous bone fractures in children: risk of meningitis, and indication for early Cochlear implant?

The case of a 5 year old boy who had a right petrous bone fracture with right CSF otorrhea and deafness is reported. This child presented, three years after the trauma, a right side otitis media, complicated by meningitis and pneumococcal sepsis, which might have as consequence a left side deafness. The bilateral deafness and the early possibility for cochlear ossification made us decide rapidly on a cochlear implant. Benjamin was then operated for a left side cochlear implant 40 days after contracting meningitis. Two months later, this boy was able to understand a speech without lip reading. Current concepts in the management of petrous bone fractures with CSF otorrhea are reviewed in this report. We also discussed prophylactic attitudes to adopt to reduce the risk of post temporal bone fracture meningitis.

The role of evoked potentials (EPs) in the assessment of the human central auditory nervous system (CANS).

This paper presents an overview of the use of EPs in the assessment of the CANS. Emphasis is laid on recent developments and research efforts centered on appraising how the auditory neural code is processed by the central pathways. It is shown how, in addition to their classical site-of-lesion testing role, EPs can, especially when combined with ecological (mostly speech-like) stimuli, yield highly valuable information on the neurophysiological processes leading to the perception of auditory objects as well as speech. Special space is devoted to the Mismatch Negativity that currently provides the only objective measure of the accuracy with which the CANS detects auditory and phonetic contrasts.

[Treatment of cleft lip and palate in the children's Hospital Reine Fabiola in Bruxelles]. / Prise en charge des fentes labio-maxillo-palatines à l'hôpital des enfants Reine Fabiola de Bruxelles.

The priority in the treatment of facial clefts is to avoid the iatrogenic sequellae by restoring a normal anatomy of the face. The difficulty of this treatment is that the majority of the sequellae are only observed 15 years after the primary treatment. After having treated our children during more than 20 years by a primary closure of the lip at 6 months and closure of the palate by push back according to Veau Wardill at 18 months, we adopted the technique of René Malek since 1981 with early closure of the palate at 3 months then, without undermining of the palatal mucosa, closure of the bony palate with a vomer flap at the age of 6 months. Since 1988, in unilateral complete cleft, we perform a complete closure of the lip and palate at 3 months according to the same surgical principles. The study of the dental casts according to the Golson Yardstick at the age of 10 and the cephalometric study by lateral Xrays at the age of 15 show an excellent facial growth in the majority of the cases with only 6% needing a osteotomy at the end of growth. Moreover the phonation of these children was very good in the majority of the cases, 15% only needing a secondary surgery. The only remaining sequellae are in the auditory field with an abnormal frequency of sero mucous otitis. These could not be improved until now despite the early use of tympanic drains.

[Cochlear implantation, new prosthetic alternative in the management of the profoundly deaf child]. / L'implant cochléaire, nouvelle alternative prothétique dans la prise en charge de l'enfant sourd profond.

Cochlear implants are new medical devices. In contrast to acoustic hearing aids which work by amplification, cochlear implants directly stimulate the hearing neurons via electrode implanted in the cochlear tympanic ramp. They are indicated in case of profound hearing deficiency or in cases of bilateral cophosis, congenital or acquired. Implanted early, they allow deaf children to improve their speech comprehension and their verbal expression considerably, thereby favouring social integration. A concurrent system of support including the use of visual-manual means of communication nevertheless remains vital for the first years. The frequency and duration of such support varies according to the individual.

Auditory neuropathy with preserved cochlear microphonics and secondary loss of otoacoustic emissions.

Auditory neuropathy is defined as absent or severely distorted auditory brainstem responses with preserved otoacoustic emissions and cochlear microphonics. This entity can be found in various circumstances including pre-lingual children. An almost universal characteristic reported from adult patients is the ineffectiveness of traditional hearing aids. Adequate management of pre-lingual cases therefore remains an open problem. This paper describes two pre-lingual children whose follow-up data demonstrated a selective loss of the otoacoustic emissions, whereas the cochlear microphonics remained preserved. In one of the patients, hearing aid fitting as soon as she lost her otoacoustic emissions proved successful. These findings have important implications for the operational definition of the condition, since one must be prepared to encounter cases with absent otoacoustic emissions. The present data also demonstrate that conventional amplification can benefit pre-lingual auditory neuropathy cases, at least once they have lost their otoacoustic emissions.

Temporal distortion products (kernel slices) evoked by maximum-length-sequences in auditory neuropathy: evidence for a cochlear pre-synaptic origin.

When special pseudo-random stimuli sequences (maximum length sequences: MLS) are combined with a deconvolution analysis technique, it is possible to derive new evoked potential components that are called kernels. The kernels give a measure of the temporal interactions that take place between the responses to successive stimuli. This may provide an objective neurophysiological test for the exploration of a dimension of hearing which has hitherto been limited to psychophysical methods. Until now, auditory short-latency kernels obtained by the MLS method have been related to the late portion of the brainstem auditory evoked potential (BAEP), suggesting that temporal interactions occur rather late in the auditory pathways. We report 4 children without any BAEP neural components, who all retained isolated cochlear microphonic potentials. Three of them produced click-evoked otoacoustic emissions and two of them demonstrated only moderately impaired audiometric thresholds. This combination of absent BAEP neural components with preserved otoacoustic emissions and cochlear microphonic potential corresponds to a peculiar pattern of auditory dysfunction recently coined "auditory neuropathy'. All 4 children exhibited well-defined kernels at latencies consistent with the microphonic potential. These data indicate that the cochlea itself can generate kernels at a presynaptic level. They open up the question of the identification of the physiological site(s) responsible for the generation of MLS-evoked kernels.

Auditory neuropathy: a report on three cases with early onsets and major neonatal illnesses.

We report 3 children without any brainstem auditory evoked potential (BAEP) neural component who all retained isolated cochlear microphonic potentials as well as click-evoked otoacoustic emissions. Two of them demonstrated only moderately impaired audiometric thresholds. These features correspond to a peculiar pattern of auditory dysfunction recently coined "auditory neuropathy'. In contrast with the published previous cases of auditory neuropathy presenting with an acquired hearing deficit as children or young adults, all 3 children had a history of major neonatal illness and the auditory neuropathy was already demonstrated in the first months of their lives.