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Otologic Manifestations of Autosomal Recessive Congenital Ichthyosis in Children
Manifestaciones otológicas en los niños con ictiosis congénitas autosómicas recesivas
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Martín-Santiago, M. Rodríguez-Pascual, N. Knöpfel, Á. Hernández-Martín" "autores" => array:4 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Martín-Santiago" "email" => array:1 [ 0 => "anahsd@telefonica.net" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Rodríguez-Pascual" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "N." "apellidos" => "Knöpfel" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Á." "apellidos" => "Hernández-Martín" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitario Son Espases, Palma de Mallorca, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Otorrinolaringología, Hospital Universitario Son Espases, Palma de Mallorca, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Infantil Universitario Niño Jesús, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Manifestaciones otológicas en los niños con ictiosis congénitas autosómicas recesivas" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1462 "Ancho" => 3001 "Tamanyo" => 591377 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Case 4. A, Collodion baby phenotype at 24<span class="elsevierStyleHsp" style=""></span>hours old. B, Marked ectropion at 3 weeks of age. C, Lamellar ichthyosis phenotype at 4 years of age.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Nonsyndromic autosomal recessive congenital ichthyosis (ARCI) is a rare hereditary keratinization disorder in which heat intolerance, pruritus, growth abnormalities, ocular and hearing disorders, and social communication deficits may also arise in addition to skin manifestations.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> The clinical course of ear complications has rarely been reported in the literature.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Objectives</span><p id="par0010" class="elsevierStylePara elsevierViewall">The objective of this study was to determine the type of otologic manifestations present in patients diagnosed with ARCI and currently in follow-up in the Pediatric Dermatology Unit of the University Hospital Son Espases, Spain.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">The presence of the following manifestations was studied prospectively: pain, ear pruritus, tinnitis, otitis, wax plug, accumulation of epithelial remnants, and deafness. The medical history included daily hygiene measures, topical treatments or medical-surgical interventions required, and frequency of visits to ear-nose-throat (ENT) specialists. All patients underwent otoscopy and hearing tests (pure tone audiometry [PTA], audiometry with visual reinforcement [AVR], and measurement of distortion products in the audiogram [DPgram]). The auditory results were calculated separately for each ear in decibels (dB). The binaural loudness was quantified using pure tone average, which is used in children and recommended by the Bureau International d’Audiophonologie (BIAP). In children who, given their age, could not perform conventional audiometry, estimates were derived from objective tests (DPgram) and behavioral tests (AVR). In these cases, hearing was considered better than 30<span class="elsevierStyleHsp" style=""></span>dB (although the true hearing could be better) when functional hearing was observed.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0020" class="elsevierStylePara elsevierViewall">The same ENT specialist examined 10 patients, 8 boys and 2 girls, aged between 11 months and 18 years. The underlying molecular deficit was identified in both patients with self-healing collodion baby (<span class="elsevierStyleItalic">TGM1</span> and <span class="elsevierStyleItalic">ALOX12B</span>) but only in 2 out of 8 patients with skin manifestations of ichthyosis (<span class="elsevierStyleItalic">ALOXE3</span> and <span class="elsevierStyleItalic">TGM1</span>) (<a class="elsevierStyleCrossRef" href="#tbl0005">Tables 1 and</a><a class="elsevierStyleCrossRef" href="#tbl0010">2</a>). Detailed medical history and the examination performed by the ENT specialist did not reveal otologic symptoms or deafness in either of the 2 cases of self-healing collodion baby. Currently, both have only minimal dermatologic manifestations, although one did have tympanic membrane retraction. All of the remaining 8 children with generalized scaling had some otologic symptom: 8 out of 8 had a history of wax plugs, 6 out of 8 had accumulation of epithelial remnants, 3 out of 8 had ear pruritus, 3 out of 8 had occasional ear pain, 2 out of 8 had otitis, and 1 out of 8 had tinnitus. None of the 8 children used topical ear products daily, only 2 out of 8 cleaned the external auditory canal (EAC) with a cotton wool bud, and 2 out of 8 had been receiving systemic treatment with acitretin for several years. Examination of the EAC of these 8 patients revealed that 2 had wax and epithelial remnants that prevented visualization of the eardrum, 3 out of 8 had scaling with or without wax with normal eardrums, 1 out of 8 had tympanic membrane retraction, and 2 did not have any abnormal findings. The hearing test showed conduction deafness in 2 patients. Ear care, with gradual cleaning and unblocking of the EAC, enabled one patient to regain hearing (case 4, <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, <a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>). Of the 10 cases studied, only 3 children had been seen regularly, at least once a year, by an ENT specialist.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">Few studies have assessed the type and severity of hearing loss in patients with ARCI. In 2014, Huang et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> published the results of surveys of 135 patients with different forms of nonsyndromic ichthyosis performed using the website of the Foundation for Ichthyosis and Related Skin Types. The results showed that 80% had ear pruritus, 66% had hearing loss, 29% had ear pain, 28% had abnormal hearing test results, and 16% used hearing aids. These manifestations were more frequent in adults (77% in respondents<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>18 years) than in patients under 18 years of age (53%).</p><p id="par0030" class="elsevierStylePara elsevierViewall">Our study is limited by the low number of patients, all under 19 years of age. However, the fact that it is prospective and that all cases were assessed by the same ENT specialist increases the reliability of the results. In our study, all patients with ichthyosis reported at least 1 sign or symptom in their medical history. In 75%, abnormalities were observed in the EAC examination, and 25% had conduction deafness, which in one case could be reversed thanks to the care routine.</p><p id="par0035" class="elsevierStylePara elsevierViewall">In 2014, Hernández-Martín et al.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> conducted a survey of members of the Spanish Ichthyosis Association to investigate the type and name of the specialists who attended patients with ichthyosis. The study showed that most of these patients were treated by physicians with little experience in ichthyosis and that they are not regularly attended by multidisciplinary teams.</p><p id="par0040" class="elsevierStylePara elsevierViewall">It is necessary to implicate ENT specialists in the management of otologic manifestations associated with ichthyosis and their potential complications.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6–8</span></a> It is essential that the dermatologist and ENT specialist participate jointly in the management of these patients to establish the best therapeutic and preventive measures (daily hygiene routine, most appropriate topical products). More studies are needed to determine the frequency of otologic involvement, the repercussion on quality of life,<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9,10</span></a> and the minimum ideal frequency for visits to the ENT specialist.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Ethical Disclosures</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Protection of human and animal subjects</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Confidentiality of data</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that they have followed their hospital's protocol on the publication of data concerning patients.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Right to privacy and informed consent</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors obtained the informed consent of patients and/or subjects mentioned in this article. The informed consent form is located in the archives of the corresponding author.</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of Interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres576318" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec592971" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres576317" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Material y método" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec592972" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Objectives" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Methods" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 9 => array:3 [ "identificador" => "sec0030" "titulo" => "Ethical Disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Right to privacy and informed consent" ] ] ] 10 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflicts of Interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-04-13" "fechaAceptado" => "2015-06-22" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec592971" "palabras" => array:5 [ 0 => "Ichthyosis" 1 => "Hearing loss" 2 => "Deafness" 3 => "Otological" 4 => "Ear, nose and throat" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec592972" "palabras" => array:5 [ 0 => "Ictiosis" 1 => "Hipoacusia" 2 => "Sordera" 3 => "Otológicas" 4 => "Otorrinolaringología" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Few studies have investigated ear involvement in nonsyndromic autosomal recessive congenital ichthyosis (ARCI).</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To assess the type and frequency of otologic manifestations of ARCI in patients under follow-up at the pediatric dermatology department of our hospital.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Materials and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We prospectively studied the presence of ear pain, ear itching, tinnitus, otitis, cerumen impaction, accumulation of epithelial debris, and hearing loss. Daily hygiene measures, topical treatments, medical-surgical interventions, and frequency of visits to an ear, nose, and throat (ENT) specialist were noted in the patients’ medical records. Ear examination and hearing tests were performed in all cases.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Ten patients were studied: 2 had a self-healing collodion baby phenotype and 8 had ichthyosis. There was mention of otologic manifestations in the records of all 8 patients with ichthyosis (100%); 6 of these patients (75%) had abnormalities in the external auditory canal examination and 2 (25%) had conductive hearing loss. Our findings are limited by the small number of patients studied, all of whom were younger than 19 years.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The involvement of both dermatologists and ENT specialists in the management of patients with ichthyosis is crucial to ensure the application of the best therapeutic and preventive measures. More studies are needed to assess the prevalence and impact on quality of life of ear involvement in patients with ichthyosis and to determine the optimal interval between ENT visits for these patients.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducción</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Las complicaciones otológicas asociadas a las ictiosis congénitas autosómicas recesivas (ICAR) no sindrómicas, apenas han sido estudiadas en la literatura.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Conocer la frecuencia y el tipo de manifestaciones otológicas de los pacientes diagnosticados de ICAR, actualmente en seguimiento en la unidad de dermatología pediátrica de nuestro hospital.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Material y método</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se estudió de forma prospectiva la presencia de los siguientes parámetros: dolor, prurito ótico, acúfenos, otitis, tapón de cerumen, acúmulo de restos epiteliales y sordera. Se recogió en la anamnesis las medidas de higiene diaria, tratamientos tópicos o intervenciones médico-quirúrgicas requeridas y la periodicidad con la que los pacientes habían consultado a un especialista de otorrinolaringología (ORL). En todos los casos se realizaron otoscopia y pruebas auditivas.</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se estudiaron 10 pacientes, 2 con fenotipo de bebé colodión autorresolutivo y 8 con ictiosis. Un 100% (8/8) de los pacientes con ictiosis referían algún síntoma o signo en la anamnesis, en el 75% (6/8) se observaron anomalías en la exploración del conducto auditivo externo y en el 25% (2/8) se objetivó sordera de conducción, que en un caso se consiguió revertir. Nuestro trabajo está limitado por el escaso número de pacientes, todos menores de 19 años.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Es fundamental la participación conjunta del dermatólogo y del especialista de ORL en el manejo de los pacientes con ictiosis para establecer las mejores medidas terapéuticas y preventivas. Se precisan más estudios que determinen la frecuencia de la afectación otológica, su repercusión en la calidad de vida y la periodicidad mínima idónea de visitas al especialista de ORL.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Material y método" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Martín-Santiago A, Rodríguez-Pascual M, Knöpfel N, Hernández-Martín Á. Manifestaciones otológicas en los niños con ictiosis congénitas autosómicas recesivas. Actas Dermosifiliogr. 2015;106:733–739.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1462 "Ancho" => 3001 "Tamanyo" => 591377 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Case 4. A, Collodion baby phenotype at 24<span class="elsevierStyleHsp" style=""></span>hours old. B, Marked ectropion at 3 weeks of age. C, Lamellar ichthyosis phenotype at 4 years of age.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1361 "Ancho" => 2583 "Tamanyo" => 387527 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Case 4: Hearing test results show basal hypoacusia and reversion after progressive extraction of wax and epithelial remnants that were obstructing the external ear canals.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: abs, antibiotic; Bi, biaural; dB, decibel; EAC, external ear canal; ENT, ear-nose-throat; LE, left ear; PTA, pure tone audiometry; RE, right ear.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case 1 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case 2 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case 3 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case 4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case 5 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case 6 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case 7 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case 8 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Molecular Studies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">de novo mutation, not previously described, of the ALOXE 3 gene \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">TGM1</span>, <span class="elsevierStyleItalic">CYP4F22</span>, <span class="elsevierStyleItalic">NIPAL4</span>, <span class="elsevierStyleItalic">ALOXE3</span>, <span class="elsevierStyleItalic">ALOX12B</span>, <span class="elsevierStyleItalic">STS</span> mutations not found. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">TGM1</span>, <span class="elsevierStyleItalic">CYP4F22</span>, <span class="elsevierStyleItalic">NIPAL4</span>, <span class="elsevierStyleItalic">ALOXE3</span>, <span class="elsevierStyleItalic">ALOX12B</span>, <span class="elsevierStyleItalic">STS</span> mutations not found. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">TGM1</span> deletion in homozygosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">TGM1</span>, <span class="elsevierStyleItalic">CYP4F22</span>, <span class="elsevierStyleItalic">NIPAL4</span>, <span class="elsevierStyleItalic">ALOXE3</span>, <span class="elsevierStyleItalic">ALOX12B</span>, <span class="elsevierStyleItalic">STS</span> mutations not found. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">TGM1</span>, <span class="elsevierStyleItalic">CYP4F22</span>, <span class="elsevierStyleItalic">NIPAL4</span>, <span class="elsevierStyleItalic">ALOXE3</span>, <span class="elsevierStyleItalic">ALOX12B</span>, <span class="elsevierStyleItalic">STS</span> mutations not found. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">TGM1</span>, <span class="elsevierStyleItalic">STS</span> mutations not found \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">TGM1</span>, <span class="elsevierStyleItalic">STS</span> mutations not found \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex/current age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female/13 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male/18 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male/12 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male/5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male/6 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male/10 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male/6 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male/17 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pain/frequency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Occasional on contact with water \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Occasional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Occasional on contact with water \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pruritus/frequency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/monthly \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Occasional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/often \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/often \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tinnitus/frequency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Occasional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Otitis/frequency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/3 times a year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/annually \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treatment if otitis present \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Topical and systemic abs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Topical abs \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prophylaxis if otitis present \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Avoid contact with water (plugs and cap) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Accumulation of epithelial remnants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes Pineal scaling \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Wax plug/frequency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/bimonthly \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/fortnightly \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/annually \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/annually \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/variable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/variable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/variable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes/variable \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prophylactic treatment if wax plug present \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypoacusia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? (at home, repetition requested) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Habitual topical treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Daily hygiene \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not habitual \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not habitual \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ear cotton wool buds \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cleaning of external scaling remnants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not habitual \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not habitual \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not habitual \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not habitual \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Otoscopy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Desquamative EAC (++) normal ear drums \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Desquamative EAC (+) normal ear drums \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Desquamative EAC (++) wax, normal ear drums \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">EAC blocked with plugs, eardrums not visible \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">EAC visible, tympanic membrane retraction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No abnormalities \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No abnormalities \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">EAC blocked with wax and epithelial remnants \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Audiometry \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal hearing (PTA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal hearing (PTA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal hearing (PTA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Conduction hypoacusia most notable in RE (PTA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Conduction hypoacusia in LE (PTA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal hearing (PTA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal hearing (PTA) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal hearing (PTA) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Audiometry (in dB) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RE:11; LE: 9; Bi: 10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RE: 12.5; LE: 14; Bi: 13.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RE: 15; LE: 12; Bi: 13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">Initial:</span> RE: 40; LE: 30; Bi: 33; <span class="elsevierStyleItalic">Final:</span> RE: 10; LE: 10; Bi: 10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RE: 12.5; LE: 41; Bi: 21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RE: 8; LE: 12; Bi: 9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RE: 14; LE: 10; Bi: 11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">RE: 12.5; LE: 10; Bi: 11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Frequency of ENT visits \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Currently none \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Annually \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Variable frequency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Every 4 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Remarks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Systemic treatment with acitretin since 9 years old \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Systemic treatment with acitretin since 11 years old Epistaxis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recovery of hearing after EAC cleaning \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Awaiting completion of hearing study Congenital duplication of distal phalanx of the thumb <span class="elsevierStyleSmallCaps">I</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Brother of case 5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Recurrent tonsillitis \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab940635.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Otologic Manifestations of Patients With Nonsyndromic Autosomal Recessive Congenital Ichthyosis.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: ARV, audiometry with visual reinforcement; dB, decibel; DPgram, audiogram of distortion products; EAC, external ear canal; ENT, ear-nose-throat.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case 9 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case 10 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Molecular Studies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Two mutations in heterozygosis in <span class="elsevierStyleItalic">TGM1</span> gene \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mutation, not previously described, in homozygosis in the <span class="elsevierStyleItalic">ALOX12B</span> gene. <span class="elsevierStyleItalic">TGM1</span>, <span class="elsevierStyleItalic">CYP4F22</span>, <span class="elsevierStyleItalic">NIPAL4</span>, <span class="elsevierStyleItalic">ALOXE3</span>, <span class="elsevierStyleItalic">ALOX12B</span>, <span class="elsevierStyleItalic">STS</span>, <span class="elsevierStyleItalic">ABCA12</span>, and PNPLA1 mutations not found. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex/current age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male/11 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female/2 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pain/frequency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pruritus/frequency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tinnitus/frequency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Otitis/frequency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treatment if otitis present \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prophylaxis if otitis present \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Accumulation of epithelial remnants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Wax plug/frequency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prophylactic treatment if wax plug present \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypoacusia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No (family environment) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Habitual topical treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Daily hygiene \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not habitual \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not habitual \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Otoscopy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No abnormalities \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">EAC visible, tympanic membrane retraction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Audiometry \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal hearing (DPgram, ARV) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Normal hearing (ARV) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Audiometry (in dB) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Threshold <<span class="elsevierStyleHsp" style=""></span>30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Threshold <<span class="elsevierStyleHsp" style=""></span>30 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Frequency of ENT visits \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Remarks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Self-healing collodion babyXerosis, increased palmoplantar lines, acral peeling \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Self-healing collodion babyPersistent xerosis, increased palmoplantar lines \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab940634.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Otologic Manifestations of Self-Healing Collodion Baby.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nonsyndromic types of ichthyoses - an update" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H. 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Bourrat" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2013.01.022" "Revista" => array:7 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2013" "volumen" => "69" "paginaInicial" => "82" "paginaFinal" => "87" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23474424" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022510X12003188" "estado" => "S300" "issn" => "0022510X" ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010600000009/v1_201511040157/S1578219015002413/v1_201511040157/en/main.assets" "Apartado" => array:4 [ "identificador" => "6155" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010600000009/v1_201511040157/S1578219015002413/v1_201511040157/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219015002413?idApp=UINPBA000044" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 10 | 15 |
| 2024 October | 72 | 44 | 116 |
| 2024 September | 89 | 35 | 124 |
| 2024 August | 99 | 102 | 201 |
| 2024 July | 96 | 35 | 131 |
| 2024 June | 95 | 53 | 148 |
| 2024 May | 95 | 32 | 127 |
| 2024 April | 69 | 21 | 90 |
| 2024 March | 88 | 49 | 137 |
| 2024 February | 65 | 37 | 102 |
| 2024 January | 46 | 43 | 89 |
| 2023 December | 60 | 19 | 79 |
| 2023 November | 74 | 31 | 105 |
| 2023 October | 54 | 24 | 78 |
| 2023 September | 75 | 32 | 107 |
| 2023 August | 57 | 28 | 85 |
| 2023 July | 49 | 33 | 82 |
| 2023 June | 55 | 21 | 76 |
| 2023 May | 78 | 33 | 111 |
| 2023 April | 53 | 13 | 66 |
| 2023 March | 45 | 29 | 74 |
| 2023 February | 61 | 30 | 91 |
| 2023 January | 42 | 19 | 61 |
| 2022 December | 62 | 47 | 109 |
| 2022 November | 46 | 25 | 71 |
| 2022 October | 37 | 21 | 58 |
| 2022 September | 27 | 53 | 80 |
| 2022 August | 47 | 35 | 82 |
| 2022 July | 52 | 43 | 95 |
| 2022 June | 46 | 33 | 79 |
| 2022 May | 99 | 41 | 140 |
| 2022 April | 104 | 36 | 140 |
| 2022 March | 67 | 47 | 114 |
| 2022 February | 50 | 22 | 72 |
| 2022 January | 91 | 42 | 133 |
| 2021 December | 56 | 32 | 88 |
| 2021 November | 63 | 50 | 113 |
| 2021 October | 106 | 44 | 150 |
| 2021 September | 60 | 34 | 94 |
| 2021 August | 58 | 22 | 80 |
| 2021 July | 51 | 33 | 84 |
| 2021 June | 61 | 32 | 93 |
| 2021 May | 52 | 29 | 81 |
| 2021 April | 199 | 40 | 239 |
| 2021 March | 105 | 26 | 131 |
| 2021 February | 67 | 29 | 96 |
| 2021 January | 58 | 17 | 75 |
| 2020 December | 51 | 19 | 70 |
| 2020 November | 26 | 19 | 45 |
| 2020 October | 43 | 25 | 68 |
| 2020 September | 32 | 14 | 46 |
| 2020 August | 25 | 17 | 42 |
| 2020 July | 27 | 19 | 46 |
| 2020 June | 52 | 33 | 85 |
| 2020 May | 17 | 15 | 32 |
| 2020 April | 28 | 25 | 53 |
| 2020 March | 22 | 19 | 41 |
| 2020 February | 4 | 1 | 5 |
| 2020 January | 0 | 1 | 1 |
| 2019 December | 4 | 4 | 8 |
| 2019 November | 1 | 2 | 3 |
| 2019 October | 0 | 4 | 4 |
| 2019 September | 4 | 3 | 7 |
| 2019 August | 0 | 1 | 1 |
| 2019 July | 0 | 1 | 1 |
| 2019 June | 2 | 28 | 30 |
| 2019 May | 0 | 18 | 18 |
| 2019 April | 0 | 8 | 8 |
| 2019 March | 2 | 4 | 6 |
| 2019 February | 1 | 4 | 5 |
| 2019 January | 10 | 0 | 10 |
| 2018 December | 4 | 2 | 6 |
| 2018 November | 1 | 0 | 1 |
| 2018 October | 2 | 3 | 5 |
| 2018 September | 7 | 2 | 9 |
| 2018 August | 0 | 4 | 4 |
| 2018 May | 0 | 3 | 3 |
| 2018 April | 0 | 1 | 1 |
| 2018 March | 1 | 0 | 1 |
| 2018 February | 60 | 7 | 67 |
| 2018 January | 79 | 4 | 83 |
| 2017 December | 75 | 10 | 85 |
| 2017 November | 24 | 4 | 28 |
| 2017 October | 32 | 3 | 35 |
| 2017 September | 16 | 14 | 30 |
| 2017 August | 30 | 18 | 48 |
| 2017 July | 35 | 13 | 48 |
| 2017 June | 39 | 27 | 66 |
| 2017 May | 28 | 13 | 41 |
| 2017 April | 28 | 10 | 38 |
| 2017 March | 16 | 43 | 59 |
| 2017 February | 71 | 14 | 85 |
| 2017 January | 40 | 12 | 52 |
| 2016 December | 24 | 9 | 33 |
| 2016 November | 52 | 14 | 66 |
| 2016 October | 31 | 27 | 58 |
| 2016 September | 0 | 1 | 1 |
| 2016 June | 4 | 3 | 7 |
| 2016 May | 4 | 1 | 5 |
| 2015 November | 0 | 8 | 8 |
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