Case study
Type 2 laryngeal cleft associated with OpitzG/BBB syndrome
Hendidura laríngea tipo 2 asociada a síndrome de Opitz G/BBB
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Sáenz-Moreno, Fernando Gómez-Sáez, Ana Navazo-Eguia" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Cristina" "apellidos" => "García-Muro" "email" => array:1 [ 0 => "cristina.garciamuro@gmail.com" ] "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" => "Isabel" "apellidos" => "Sáenz-Moreno" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Fernando" "apellidos" => "Gómez-Sáez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Ana" "apellidos" => "Navazo-Eguia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Pediatría, Hospital San Pedro, Logroño, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Cuidados Intensivos Pediátricos, Hospital Universitario de Burgos, Burgos, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Otorrinolaringología, Hospital Universitario de Burgos, Burgos, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hendidura laríngea tipo 2 asociada a síndrome de Opitz G/BBB" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1657 "Ancho" => 1508 "Tamanyo" => 121779 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Laryngeal cleft extending into the lower region of the cricoid cartilage. Type 2 according to the Benjamin-Inglis classification.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Case study</span><p id="par0005" class="elsevierStylePara elsevierViewall">We present the case of a 4-year-old patient with stridor and severe difficulty in breathing, who required admission to a Paediatric ICU and invasive ventilation. Bronchoscopy examination revealed a type 2 laryngeal image according to the Benjamin Inglis classification (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) (Appendix A, Video 1 of additional material). Endoscopic correction was performed with reconstruction of the cleft by suture in both planes (oesophageal and laryngotracheal), with interposition of fascial muscle lamina from the sternocleidomastoid muscle between both lines of suture. A repeat intervention was required after 15 days due to a new episode of stridor and respiratory difficulty due to obstruction of the airway by redundant inter-arytenoid tissue. This was resolved by diode laser photocoagulation of the oesophageal mucus swelling, with good subsequent evolution.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">The following aspects stand out within the clinical history of our patient: diagnosis at one month of life of laryngotracheomalacia by nasofibroscopy, without other complications. There were also hypospadias, cryptorchidy and umbilical hernia. He was diagnosed persistent arterial ductus, which closed spontaneously at one year of life, and he required monitoring by the Neuropaediatric Unit due to hypotonia at breast feeding age, as well as having a peculiar phenotype with hypertelorism and left ptosis. Given all of the said factors, and following the diagnosis of laryngeal cleft, the suspicion of Opitz G/BBB syndrome was established, and it was confirmed by the finding of the hemizygotic c.346A >T mutation in the MID1 gene.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Discussion</span><p id="par0015" class="elsevierStylePara elsevierViewall">Laryngeal clefts (LC) are rare congenital anomalies of the airways and digestive tract, with an incidence of 1/10,000–20,000 live new births, with a slight predominance of the male sex.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> They consist of the incomplete separation between the oesophagus and the airway from the start of the larynx.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">LC is a rare pathology that is caused by an incomplete formation of the tracheoesophageal septum during embryonic development. Depending on the severity of this defect, different anomalies may be produced such as an isolated laryngeal cleft, a tracheoesophageal fistula or oesophageal atresia.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Clinical manifestations vary depending on the depth of the LC.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> There are several different classifications of laryngeal clefts, of which the most widely used is the one by Benjamin-Inglis,<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,5</span></a> which differentiates 4 types of laryngeal cleft according to their extension. Types 1 and 2 usually present with mild respiratory symptoms and difficulty in eating, with frequent aspirations.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,3</span></a> It is striking that the patient in the case described, with type 2 LC, had no respiratory symptoms during the first years of life, and commenced with an episode of severe respiratory difficulty at the age of 4 years. Types 3 and 4 are more severe forms, with a more extensive communication between the oesophagus and the trachea.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Symptoms commence in these forms in the neonatal period, with severe respiratory alterations,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,4,6</span></a> and they generally require early bronchoscopy due to episodes of apnoea and hypoxia.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The diagnostic method of choice is direct laryngoscopy.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> It is important to take this pathology into account in the differential diagnosis of children with stridor, recurring respiratory infections and alterations in deglutition.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,6</span></a> Bronchoscopy makes it possible to classify and describe the extension of the defect, and it was the key to diagnosis in the case described.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The treatment of LC is medical as well as surgical.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In medical terms, it is fundamental to prevent pulmonary complications associated with aspiration episodes, ensuring appropriate nutrition and using thickeners when this is necessary.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,7</span></a> It is also important to treat other comorbidities (gastric-oesophageal reflux, bronchial hyper-reactivity or food allergies, etc.) which may affect the airway and digestive tract.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> Medical treatment is especially important in type 1 LC, given that some authors state that appropriate medical treatment in these cases may delay or avoid the need for surgical repair.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,4</span></a> For surgical treatment, the access approach will depend on the type of cleft to be treated. In types 1 and 2 endoscopic repair of the laryngeal defect is preferred, reserving open surgery for types 3 and 4, together with those cases in which endoscopic technique was unsuccessful or failed.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Although the majority of LC cases are isolated, they may also be associated with other congenital alterations, of which the most common are midline defects (cardiac, genital-urinary or gastrointestinal anomalies).<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The presence of a LC in association with other defects should make us consider certain specific syndromes, as it has been associated with the CHARGE, Pallister-Hall, VACTERL and Opitz G/BBB syndromes, as it was in the case described.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2,4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Given that our patient had several congenital anomalies associated with LC, a genetic study was undertaken which finally confirmed the diagnosis of Opitz-G/BBB syndrome. This syndrome was described for the first time by Opitz in 1969,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and up to 30% of the patients affected have a LC.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> The majority of the anomalies associated with this syndrome also affect the midline (hypertelorism, hypospadias, cardiac alterations, cleft palate …) suggesting that the mutation mainly affects morphogenic processes at this level.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> There are two clinically indistinguishable genetic subtypes of the Opitz-G/BBB syndrome: one variant linked to chromosome X and another dominant autosomal variant.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The first of these variants is the most common, even though its frequency in the population is extremely low (1/100,000 new-born babies), and it is associated with mutations in the MID1 (Xp22) gene.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> The c.346A >T mutation, which was found in our case, has not been described beforehand in databases. Nevertheless, and given its nature, it is considered to be pathological and able in itself to explain the Opitz-G/BBB phenotype. As this syndrome is linked to chromosome X, only males develop this disease. Carrier women usually have hypertelorism as the sole manifestation, and the mother of the patient had this characteristic. However, genetic diagnosis of the parents was not performed as the family refused this.</p><p id="par0050" class="elsevierStylePara elsevierViewall">To conclude, we should underline that LC are a rare anomaly which requires a high level of suspicion for diagnosis, especially in types 1 and 2, as they have symptoms which may often be confused with other diseases. Moreover, given that this pathology is often associated with certain syndromes, a genetic study should be considered in patients with other associated anomalies.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Authorship /collaborators</span><p id="par0055" class="elsevierStylePara elsevierViewall">All of the authors express their agreement with the work produced and state that they actively collaborated in preparing the same.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Conflict of interests</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Case study" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Discussion" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Authorship /collaborators" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflict of interests" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-03-14" "fechaAceptado" => "2021-05-02" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: García-Muro C, Sáenz-Moreno I, Gómez-Sáez F, Navazo-Eguia A. Hendidura laríngea tipo 2 asociada a síndrome de Opitz G/BBB. Acta Otorrinolaringol Esp. 2022;73:196–198.</p>" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0070" class="elsevierStylePara elsevierViewall">The following is Supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0030" ] ] ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1657 "Ancho" => 1508 "Tamanyo" => 121779 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Laryngeal cleft extending into the lower region of the cricoid cartilage. Type 2 according to the Benjamin-Inglis classification.</p>" ] ] 1 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:3 [ "fichero" => "mmc1.mp4" "ficheroTamanyo" => 6074094 "Video" => array:2 [ "mp4" => array:5 [ "fichero" => "mmc1.m4v" "poster" => "mmc1.jpg" "tiempo" => 0 "alto" => 0 "ancho" => 0 ] "flv" => array:5 [ "fichero" => "mmc1.flv" "poster" => "mmc1.jpg" "tiempo" => 0 "alto" => 0 "ancho" => 0 ] ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Laryngotracheoesophageal clefts" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.E. Strychowsky" 1 => "R. 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|---|---|---|---|
| 2024 November | 1 | 0 | 1 |
| 2024 October | 25 | 0 | 25 |
| 2024 September | 45 | 0 | 45 |
| 2024 August | 36 | 0 | 36 |
| 2024 July | 34 | 0 | 34 |
| 2024 June | 19 | 1 | 20 |
| 2024 May | 11 | 0 | 11 |
| 2024 April | 19 | 0 | 19 |
| 2024 March | 35 | 0 | 35 |
| 2024 February | 68 | 0 | 68 |
| 2024 January | 41 | 0 | 41 |
| 2023 December | 73 | 0 | 73 |
| 2023 November | 59 | 0 | 59 |
| 2023 October | 74 | 2 | 76 |
| 2023 September | 43 | 0 | 43 |
| 2023 August | 31 | 0 | 31 |
| 2023 July | 80 | 0 | 80 |
| 2023 June | 59 | 2 | 61 |
| 2023 May | 95 | 0 | 95 |
| 2023 April | 45 | 0 | 45 |
| 2023 March | 40 | 0 | 40 |
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| 2023 January | 29 | 1 | 30 |
| 2022 December | 49 | 0 | 49 |
| 2022 November | 47 | 2 | 49 |
| 2022 October | 35 | 0 | 35 |
| 2022 September | 42 | 0 | 42 |
| 2022 August | 30 | 0 | 30 |
| 2022 July | 37 | 0 | 37 |
| 2022 June | 41 | 0 | 41 |
| 2022 May | 17 | 0 | 17 |
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