Case and Research Letters
Self-healing Collodion Baby: A New Mutation in the ALOX12B Gene
Bebé colodión autorresolutivo: nueva mutación en el gen ALOX12B
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Membrana brillante que cubre a modo de coraza la práctica totalidad de la superficie corporal. B. Ectropión, eclabium y manos en garra. C. Retracción del pabellón auricular izquierdo y membrana en la espalda con fisura en la zona central dorsal. D. Descamación en grandes láminas que afecta a toda la membrana.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "R. Santesteban Muruzábal, A. Larumbe Irurzun, I. Yanguas Bayona, M.A. Ramos Arroyo" "autores" => array:4 [ 0 => array:2 [ "nombre" => "R." "apellidos" => "Santesteban Muruzábal" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Larumbe Irurzun" ] 2 => array:2 [ "nombre" => "I." 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Santesteban Muruzábal, A. Larumbe Irurzun, I. Yanguas Bayona, M.A. Ramos Arroyo" "autores" => array:4 [ 0 => array:4 [ "nombre" => "R." "apellidos" => "Santesteban Muruzábal" "email" => array:1 [ 0 => "raquel.santesteban@hotmail.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" => "A." "apellidos" => "Larumbe Irurzun" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "I." "apellidos" => "Yanguas Bayona" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "M.A." "apellidos" => "Ramos Arroyo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Complejo Hospitalario de Navarra, Pamplona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Genética, Complejo Hospitalario de Navarra, Pamplona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Bebé colodión autorresolutivo: nueva mutación en el gen ALOX12B" ] ] "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" => 1201 "Ancho" => 1600 "Tamanyo" => 387266 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Shiny membrane covering practically the whole body surface like a suit of armor. B, Ectropion, eclabium, and clawed-hand deformity. C, Retraction of the auricle of the left ear and view of the membrane over the back with a central fissure in the dorsal region. D, Peeling of the whole membrane in large sheets.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We present the case of a newborn infant born preterm at 36 weeks, with no family history of interest, diagnosed in utero with eclabium and ectropion, with a suspected diagnosis of harlequin fetus. At birth, the infant presented a membrane that covered practically the whole body surface like a suit of armor (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A), in addition to ectropion, eclabium, clawed-hand deformity (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B), and retraction of the auricles of both ears (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C). During the first days after delivery, the membrane fissured and subsequently peeled away in large sheets (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>D), leaving the underlying skin erythematous and exudative; the membrane had fallen completely by the second week of life. The clinical course was very good over the following months, and at 1 year the skin had a practically normal appearance (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A), showing only mild erythema and peeling on both cheeks (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>B) and minimal hyperkeratosis on the elbows and knees. A diagnosis of self-healing collodion baby (CB) was made. Genetic analysis showed the child to be a homozygous carrier of a mutation in the <span class="elsevierStyleItalic">ALOX12B</span> gene that produced loss of an amino acid, glutamine, at position 136 of exon 3; the parents were healthy heterozygous carriers of this mutation. At the time of writing this article, the patient was 2 years of age and had no lesions except those commented above.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">CB presents at birth with a tight, shiny, transparent, armor-like membrane that covers the whole body surface and looks like cellophane wrapping.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> This can give rise to ectropion, eclabium, pseudocontractures, absence of eyebrows, sparse hair, and hypoplasia of the nasal and auricular cartilage.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> The membrane is inelastic, so the child's breathing and movements after birth provoke fissuring, and it then peels away in large sheets and is completely lost by 2 to 4 weeks of life.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> CB is a rare condition, with an incidence between 1 in 50<span class="elsevierStyleHsp" style=""></span>000 to 1 in 100<span class="elsevierStyleHsp" style=""></span>000 births. It is the initial clinical manifestation of a number of genetic diseases, the majority of which belong to the group of autosomal recessive congenital ichthyoses (ARCI).<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> CB can develop into very diverse phenotypes, from skin with a normal appearance to intense ichthyosis; the majority of patients are diagnosed with lamellar ichthyosis or congenital ichthyosiform erythroderma.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,3</span></a> Self-resolving CB is a minor form of ARCI.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Between 10% and 24% of cases of CB are self-resolving; these are cases that show spontaneous resolution of the condition and in adult life present a normal skin or discreet signs of ichthyosis.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,5</span></a> Regarding the epidemiology of ARCI, Hernández-Martín et al., in Spain, published a study in which the estimated prevalence of ARCI was of approximately 16 cases per million population, with a prevalence of self-resolving CB of 4.2% in the overall ARCI population.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Self-resolving CB has been associated with mutations in genes <span class="elsevierStyleItalic">TGM1</span>, <span class="elsevierStyleItalic">ALOXE3</span>, and <span class="elsevierStyleItalic">ALOX12B</span>.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,3–5,7</span></a> Our patient was diagnosed as a homozygous carrier of a mutation in gene <span class="elsevierStyleItalic">ALOX12B</span> that has not previously been described in the literature. The <span class="elsevierStyleItalic">ALOX12B</span> gene was first identified in 2002. It is formed of 15 exons and codes for the epidermal lipoxygenases eLOX-3 and 12R-LOX.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Its predominant expression in the suprabasal layers of the epidermis supports its role in the advanced phases of epidermal differentiation and its participation in processing lamellar bodies. In addition, it acts in the hepoxilin pathway and is therefore thought possibly to participate in the formation of the intercellular lipids of the corneal layer or to act in signaling to promote keratinocyte differentiation.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">More than 30 mutations of the <span class="elsevierStyleItalic">ALOX12B</span> gene have been described since its identification and, together with gene <span class="elsevierStyleItalic">ALOXE3</span>, it is considered responsible for 14% to 17% of ARCIs and for 72.2% of cases of self-resolving CB.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> The specific mechanism that leads to the changes in skin permeability in patients with alterations of gene <span class="elsevierStyleItalic">ALOX12B</span>, and the reason for the appearance of lesions in the neonatal period in self-resolving CB, are not fully understood.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> It has been postulated that these mutations of <span class="elsevierStyleItalic">ALOX12B</span> reduce enzyme activity in utero, but not after birth.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Hydrostatic pressure is high in the uterus, and the chelation of water molecules deforms the mutated enzyme into an inactive conformation. After birth, with a lower hydrostatic pressure, the enzyme returns to its active form and increases its activity to levels sufficient to maintain a normal or minimally altered phenotype.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">CB usually causes premature delivery, with increased perinatal morbidity and mortality. Important complications include increased transepidermal water loss (up to 7 times the loss from healthy skin), temperature instability, hypothermia, hypernatremic dehydration, feeding difficulties, hypohidrosis, cutaneous and systemic infections, ectropion, keratitis, and obstruction of the external auditory meatus.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2,5,10</span></a> Furthermore, the membrane can produce mechanical compression that may lead to distal limb ischemia.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The management of CB must be undertaken in a neonatal intensive care unit. Humidity in the incubator should be at least 60%, with temperature control, monitoring of electrolytes, energy supplementation, and insertion of a nasogastric tube if feeding is compromised. Although prophylactic antibiotics are not recommended, very close monitoring must be performed and antibiotic therapy initiated early if signs of infection develop.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> The use of emollients reduces transepidermal water loss and its related complications, though health staff must perform adequate hand washing and hygiene prior to applying the agents in order to reduce the risk of infection, as this has been related to the application of emollients in some reports.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Mortality in CB is currently around 5%; in 1960 it was estimated to be around 50%.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,10</span></a> It is believed that the marked improvement in prognosis is due to the advances in neonatal care.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Reporting this new case of CB is important because of its progression to self-resolving CB, a very rare entity. Self-resolving CB is a challenge not because of diagnostic problems, but rather because of the difficulty in establishing a long-term prognosis, as it is impossible to say whether a case will be a true self-resolving CB or whether it will, in contrast, develop into a very severe disease. Furthermore, the genetic analysis performed on our patient detected a mutation in the <span class="elsevierStyleItalic">ALOX12B</span> gene that had not previously been described in the literature as a mutation confirmed to cause self-resolving CB.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Muruzábal RS, Irurzun AL, Bayona IY, Arroyo MAR. Bebé colodión autorresolutivo: nueva mutación en el gen ALOX12B. Actas Dermosifiliogr. 2016;107:433–435.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1201 "Ancho" => 1600 "Tamanyo" => 387266 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Shiny membrane covering practically the whole body surface like a suit of armor. B, Ectropion, eclabium, and clawed-hand deformity. C, Retraction of the auricle of the left ear and view of the membrane over the back with a central fissure in the dorsal region. D, Peeling of the whole membrane in large sheets.</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" => 558 "Ancho" => 1604 "Tamanyo" => 123746 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A and B, Normal skin at age 1 year, with only mild erythema and peeling on the cheeks.</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:3 [ "comentario" => "169-169e1" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Self-healing collodion baby" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Theiler" 1 => "C. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 14 | 13 | 27 |
| 2024 October | 109 | 61 | 170 |
| 2024 September | 130 | 37 | 167 |
| 2024 August | 160 | 96 | 256 |
| 2024 July | 109 | 65 | 174 |
| 2024 June | 97 | 51 | 148 |
| 2024 May | 129 | 50 | 179 |
| 2024 April | 108 | 53 | 161 |
| 2024 March | 108 | 41 | 149 |
| 2024 February | 94 | 38 | 132 |
| 2024 January | 111 | 47 | 158 |
| 2023 December | 152 | 33 | 185 |
| 2023 November | 155 | 43 | 198 |
| 2023 October | 128 | 41 | 169 |
| 2023 September | 106 | 43 | 149 |
| 2023 August | 103 | 36 | 139 |
| 2023 July | 131 | 51 | 182 |
| 2023 June | 128 | 30 | 158 |
| 2023 May | 144 | 42 | 186 |
| 2023 April | 88 | 60 | 148 |
| 2023 March | 68 | 28 | 96 |
| 2023 February | 49 | 40 | 89 |
| 2023 January | 33 | 34 | 67 |
| 2022 December | 60 | 46 | 106 |
| 2022 November | 57 | 44 | 101 |
| 2022 October | 68 | 39 | 107 |
| 2022 September | 87 | 62 | 149 |
| 2022 August | 41 | 43 | 84 |
| 2022 July | 35 | 57 | 92 |
| 2022 June | 41 | 39 | 80 |
| 2022 May | 118 | 54 | 172 |
| 2022 April | 167 | 44 | 211 |
| 2022 March | 156 | 62 | 218 |
| 2022 February | 121 | 37 | 158 |
| 2022 January | 153 | 48 | 201 |
| 2021 December | 80 | 42 | 122 |
| 2021 November | 74 | 45 | 119 |
| 2021 October | 96 | 50 | 146 |
| 2021 September | 69 | 45 | 114 |
| 2021 August | 66 | 33 | 99 |
| 2021 July | 57 | 38 | 95 |
| 2021 June | 67 | 23 | 90 |
| 2021 May | 119 | 38 | 157 |
| 2021 April | 132 | 97 | 229 |
| 2021 March | 83 | 36 | 119 |
| 2021 February | 87 | 24 | 111 |
| 2021 January | 51 | 16 | 67 |
| 2020 December | 66 | 18 | 84 |
| 2020 November | 48 | 27 | 75 |
| 2020 October | 69 | 18 | 87 |
| 2020 September | 38 | 17 | 55 |
| 2020 August | 33 | 15 | 48 |
| 2020 July | 33 | 14 | 47 |
| 2020 June | 32 | 37 | 69 |
| 2020 May | 52 | 20 | 72 |
| 2020 April | 25 | 20 | 45 |
| 2020 March | 13 | 19 | 32 |
| 2020 February | 9 | 1 | 10 |
| 2019 December | 4 | 0 | 4 |
| 2019 September | 4 | 0 | 4 |
| 2019 June | 2 | 0 | 2 |
| 2019 April | 0 | 1 | 1 |
| 2019 March | 2 | 3 | 5 |
| 2019 January | 2 | 0 | 2 |
| 2018 December | 3 | 0 | 3 |
| 2018 October | 3 | 0 | 3 |
| 2018 September | 4 | 0 | 4 |
| 2018 February | 30 | 4 | 34 |
| 2018 January | 45 | 4 | 49 |
| 2017 December | 60 | 7 | 67 |
| 2017 November | 47 | 6 | 53 |
| 2017 October | 54 | 10 | 64 |
| 2017 September | 48 | 11 | 59 |
| 2017 August | 34 | 3 | 37 |
| 2017 July | 37 | 6 | 43 |
| 2017 June | 48 | 9 | 57 |
| 2017 May | 28 | 11 | 39 |
| 2017 April | 30 | 6 | 36 |
| 2017 March | 27 | 5 | 32 |
| 2017 February | 63 | 9 | 72 |
| 2017 January | 23 | 6 | 29 |
| 2016 December | 41 | 27 | 68 |
| 2016 November | 26 | 33 | 59 |
| 2016 October | 26 | 25 | 51 |
| 2016 July | 1 | 6 | 7 |
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