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array:24 [ "pii" => "S2173579421001663" "issn" => "21735794" "doi" => "10.1016/j.oftale.2020.11.018" "estado" => "S300" "fechaPublicacion" => "2022-01-01" "aid" => "1894" "copyright" => "Sociedad Española de Oftalmología" "copyrightAnyo" => "2021" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Soc Esp Oftalmol. 2022;97:44-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0365669121000101" "issn" => "03656691" "doi" => "10.1016/j.oftal.2020.11.028" "estado" => "S300" "fechaPublicacion" => "2022-01-01" "aid" => "1894" "copyright" => "Sociedad Española de Oftalmología" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Soc Esp Oftalmol. 2022;97:44-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Comunicación corta</span>" "titulo" => "Mutación del gen <span class="elsevierStyleItalic">CTNNB1</span> asociada a alteración del neurodesarrollo, microcefalia y persistencia del vítreo primario hiperplásico bilateral: reporte de un caso y revisión de la literatura" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "44" "paginaFinal" => "47" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "CTNNB1 gene mutation associated with neurodevelopmental disorder, microcephaly, and persistence of bilateral hyperplastic primary vítreous: a case report and literature review" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 666 "Ancho" => 1340 "Tamanyo" => 84426 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Ecografía ocular con transductor de 10 MHz (equipo compact touch). <span class="elsevierStyleBold">A) Ojo derecho</span>: cavidad vítrea con múltiples opacidades de reflectividad variable, mayormente altas. Longitud axial: 14,17 mm. No hay masas intraoculares. <span class="elsevierStyleBold">B)</span><span class="elsevierStyleBold">Ojo izquierdo</span>: imagen de baja reflectividad que sale del nervio óptico hacia la parte anterior. Longitud axial: 16,14 mm. No hay masas intraoculares. Concepto: Desprendimiento de retina en ojo derecho, en ambos ojos con microftalmos y persistencia del vítreo primario hiperplásico.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L.M. Zuluaga Gómez, S.C. Caballero Mojica, G.J. Vélez Rengifo, J.D. Bravo Acosta, J.H. Montoya Villada" "autores" => array:5 [ 0 => array:2 [ "nombre" => "L.M." "apellidos" => "Zuluaga Gómez" ] 1 => array:2 [ "nombre" => "S.C." "apellidos" => "Caballero Mojica" ] 2 => array:2 [ "nombre" => "G.J." "apellidos" => "Vélez Rengifo" ] 3 => array:2 [ "nombre" => "J.D." "apellidos" => "Bravo Acosta" ] 4 => array:2 [ "nombre" => "J.H." "apellidos" => "Montoya Villada" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173579421001663" "doi" => "10.1016/j.oftale.2020.11.018" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579421001663?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669121000101?idApp=UINPBA00004N" "url" => "/03656691/0000009700000001/v2_202201261000/S0365669121000101/v2_202201261000/es/main.assets" ] ] "itemSiguiente" => array:18 [ "pii" => "S2173579421001808" "issn" => "21735794" "doi" => "10.1016/j.oftale.2020.12.016" "estado" => "S300" "fechaPublicacion" => "2022-01-01" "aid" => "1901" "copyright" => "Sociedad Española de Oftalmología" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Soc Esp Oftalmol. 2022;97:48-51" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Short communication</span>" "titulo" => "Congenital hypertrophy of the retinal pigment epithelium associated with acquired retinoschisis and microcystic degeneration: The importance of multimodal imaging" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "48" "paginaFinal" => "51" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hipertrofia congénita del epitelio pigmentario de la retina asociada a retinosquisis adquirida y degeneración microquística: La importancia del estudio con imagen multimodal" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1117 "Ancho" => 1591 "Tamanyo" => 143655 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Widefield FFA shows, in late phase, a hyperfluorescent pattern due to staining of the pigmented borders of the CHRPE (white arrow), as well as hyperfluorescence due to accumulation of microcystic degeneration (yellow arrow).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Jorge Fernández-Engroba, Rafael Ollero, Anna Soldevila" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Jorge" "apellidos" => "Fernández-Engroba" ] 1 => array:2 [ "nombre" => "Rafael" "apellidos" => "Ollero" ] 2 => array:2 [ "nombre" => "Anna" "apellidos" => "Soldevila" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579421001808?idApp=UINPBA00004N" "url" => "/21735794/0000009700000001/v2_202201260939/S2173579421001808/v2_202201260939/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173579421001596" "issn" => "21735794" "doi" => "10.1016/j.oftale.2020.11.014" "estado" => "S300" "fechaPublicacion" => "2022-01-01" "aid" => "1881" "copyright" => "Sociedad Española de Oftalmología" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Soc Esp Oftalmol. 2022;97:40-3" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Short communication</span>" "titulo" => "Visual acuity loss and sixth nerve palsy as the only manifestations of slit ventricle syndrome" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "40" "paginaFinal" => "43" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Pérdida de agudeza visual y parálisis de VI nervio craneal como únicas manifestaciones de un síndrome de colapso ventricular" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1535 "Ancho" => 1583 "Tamanyo" => 81180 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Postoperative image. Axial T1 MRI, showing totally collapsed lateral ventricles (black arrows) and bilateral frontal drainage valve (yellow arrows). The brain showed no findings suggestive of elevated intracranial pressure.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "V.M. Asensio-Sánchez, G.E. Pacheco-Callirgos, J. Valentín-Bravo, L. García-Onrubia" "autores" => array:4 [ 0 => array:2 [ "nombre" => "V.M." "apellidos" => "Asensio-Sánchez" ] 1 => array:2 [ "nombre" => "G.E." "apellidos" => "Pacheco-Callirgos" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Valentín-Bravo" ] 3 => array:2 [ "nombre" => "L." "apellidos" => "García-Onrubia" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S036566912030486X" "doi" => "10.1016/j.oftal.2020.11.016" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S036566912030486X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579421001596?idApp=UINPBA00004N" "url" => "/21735794/0000009700000001/v2_202201260939/S2173579421001596/v2_202201260939/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Short communication</span>" "titulo" => "CTNNB1 gene mutation associated with neurodevelopmental disorder, microcephaly, and persistence of bilateral hyperplastic primary vitreous: A case report and literature review" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "44" "paginaFinal" => "47" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "L.M. Zuluaga Gómez, S.C. Caballero Mojica, G.J. Vélez Rengifo, J.D. Bravo Acosta, J.H. Montoya Villada" "autores" => array:5 [ 0 => array:3 [ "nombre" => "L.M." "apellidos" => "Zuluaga Gómez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "S.C." "apellidos" => "Caballero Mojica" "email" => array:1 [ 0 => "silviaccm05@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "G.J." "apellidos" => "Vélez Rengifo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "J.D." "apellidos" => "Bravo Acosta" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "J.H." "apellidos" => "Montoya Villada" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro especializado en Neurología y Psiquiatría Infantil (CENPI), Medellín, Colombia" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Hospital universitario San Vicente Fundación, Medellín, Colombia" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Mutación del gen <span class="elsevierStyleItalic">CTNNB1</span> asociada a alteración del neurodesarrollo, microcefalia y persistencia del vítreo primario hiperplásico bilateral: reporte de un caso y revisión de la literatura" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 666 "Ancho" => 1340 "Tamanyo" => 84426 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Ocular ultrasound with a 10 MHz transducer (compact touch equipment). <span class="elsevierStyleBold">A) Right eye</span>: vitreous cavity with multiple opacities of variable reflectivity, mostly high. Axial length: 14.17 mm. no intraocular masses were found. <span class="elsevierStyleBold">B) Left eye</span>: low reflectivity image anteriorly exiting the optic nerve. Axial length: 16.14 mm. No intraocular masses were found. Concept: Right eye retinal detachment, microphthalmos and hyperplastic primary vitreous persistence in both eyes.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">CTNNB1</span> gene encodes a B-catenin 1 protein that is part of the adherent junctions between cadherins and the actin cytoskeleton. This protein binds and maintains epithelial layers, cadherins and the actin cytoskeleton, allowing adhesion, communication and signaling between neighboring cells. It also plays an important role in the Wnt signaling pathway, essential for embryonic development and tissue homeostasis in adult human life.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">It is well known that increased <span class="elsevierStyleItalic">CTNNB1</span> gene expression due to degradation deregulation in somatic cells is associated to metastatic tumorigenesis, with examples such as endometrioid carcinoma, colon adenocarcinoma and breast and stomach carcinoma, among others. However, in recent years it has been described that mutations that lead to loss of function in the <span class="elsevierStyleItalic">CTNNB1</span> gene function loss during embryogenesis were associated to cognitive disability; subsequently, in reports and case series other syndromic phenotypic characteristics have been described, such as: microcephaly, facial alterations, motor and speech delay, trunk hypotonia with peripheral hypertonia, behavioral alterations and eye defects.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical case</span><p id="par0015" class="elsevierStylePara elsevierViewall">Two-month-old male patient of non-consanguineous Colombian parents, healthy with no risk factors, result of an uncomplicated first pregnancy, born by eutocic delivery at 35 weeks with a weight of 2.200 g, received supplemental oxygen for 23 days (with nasal cannula and CPAP). Due to prematurity and oxygen use the case required visual screening, in which bilateral leukocoria was evidenced. Initially retinopathy of prematurity was suspected, so an ocular ultrasound was requested.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The right eye ultrasound showed vitreous cavity with multiple mobile opacities of variable reflectivity and the left eye presented a high reflectivity image exiting the optic nerve towards the anterior part compatible with retinal detachment in both eyes, absence of mass, axial length 14.17 mm in the right eye and 16.14 mm in the left eye. These findings suggest bilateral persistent primary vitreous hyperplasia (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Due to the findings described in the ocular ultrasound, examination under general anesthesia was decided, observing: in the right eye, cornea with mild opacity, atalamy, iridocrystalline diaphragm completely displaced forward, iris with transillumination areas and neovessels extending up to the pupillary sphincter and anterior lens capsule associated with retinal detachment. In the left eye open funnel retinal detachment with tractional bands and coagulated hemorrhages (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) were observed. Intraocular pressure (IOP) was 3 mmHg in the right eye and 4 mmHg in the left eye.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Magnetic resonance imaging (MRI) with contrast evidenced eyeball changes with microphthalmia in the right eye and optic nerve atrophic changes with retinal detachment and hyaloid canal persistence without masses in the left eye; thus confirming bilateral primary vitreous hyperplasia. The other MRI findings were within normal range (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The patient was referred to pediatric neurology at three months of age due to neurodevelopmental delay and microcephaly, where the last evaluation performed describes that at 12 months of age the patient still had not achieved sitting upright, lacked good reflexes and exhibited axial and appendicular hypotonia.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Since this patient exhibited bilateral ocular development alterations not explained by gestational age and associated to systemic alterations, medical genetics initially suspected a Norrie disease gene (NDP gene) alteration however, hearing loss was ruled out and by means of <span class="elsevierStyleItalic">microarrays</span> chromosomal rearrangements were discarded, therefore it was decided to perform exome sequencing.</p><p id="par0045" class="elsevierStylePara elsevierViewall">A trio clinical exome analysis (in both the patient and parents) was performed to investigate autosomal recessive or <span class="elsevierStyleItalic">de novo</span> diseases. In this examination, DNA was extracted and quantified; bioinformatic analysis was carried out with the «Directed exome analysis» algorithm of Sistemas Genónicos SL, in which genes associated with diseases were selected in the OMIM, HGMD, HPO databases. Analyses of variants with deleterious effect, <span class="elsevierStyleItalic">de novo</span> variants and variants described as pathogenic or probably pathogenic were performed in the HGMD, NCBI ClinVar bases.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The test was positive due to the presence of a <span class="elsevierStyleItalic">de novo</span> heterozygous variant of the <span class="elsevierStyleItalic">CTNNB1</span> gene that codes for B-catenin 1 (variant: c.896_899del - p.Asp299Alafs *5, classified as pathogenic, confirmed with Sanger sequencing). In the literature, this mutation has been associated to <span class="elsevierStyleBold">Neurodevelopmental Disorder with spastic diplegia and visual defects</span> (# OMIM 615075) with an autosomal dominant inheritance pattern, which is the current diagnosis of the patient. The parents did not have this mutation.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Parents were informed and counseled on the patient's diagnosis and poor visual prognosis, and he is currently in therapy in the low vision program.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">The reported case involves a two-month-old infant patient with primary vitreous hyperplasia (ultrasound, imaging and clinical diagnosis), retinal detachment, corneal opacity, axial and appendicular hypotonia, microcephaly and neurodevelopmental delay with no brain alterations on magnetic resonance imaging. Exome sequencing was performed, finding a pathogenic de novo haploinsufficiency in the <span class="elsevierStyleItalic">CTNNB1</span> gene.</p><p id="par0065" class="elsevierStylePara elsevierViewall">B-catenin 1 protein has 781 amino acids and is encoded by the <span class="elsevierStyleItalic">CTNNB1</span> gene, found on chromosome 3 (3p22.1). It has 16 exons and belongs to the gene family that contains an armadillo repeat that controls embryonic development, relevant to the Wnt signaling pathway and cell adhesion.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In embryogenesis, the hyaloid system forms the primary vitreous during the first four to five weeks of intrauterine life and starts to regress during the secondary vitreous formation in week nine to ten. At the end of the third month, the secondary vitreous fills most of the vitreous cavity and the primary vitreous condenses into a narrow band (Cloquet's canal) that extends from the optic nerve to the posterior side of the lens.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> The persistence mechanism of the hyperplastic primary vitreous is unknown, but it has been associated to alterations in the Wnt signaling pathway, responsible for normal retinal angiogenesis and hyaloid canal regression (especially in bilateral vitreous hyperplasia and other retinal vascular alterations cases).</p><p id="par0075" class="elsevierStylePara elsevierViewall">The most common consultation reasons for primary vitreous hyperplasia are leukocoria, microphthalmos, cataract and strabismus; and the finding is usually sporadic, unilateral, non-heritable in healthy patients and in term, thus bilateral cases are rare and usually appear along systemic and neurological alterations. Therefore, other syndromic conditions have to be ruled out, mainly Norrie's disease (NDP gene on X chromosome) with variable ocular findings including primary vitreous hyperplasia and microphthalmos, together with cognitive deficit in one third of patients and sensorineural hearing loss in varying degrees. Some disorders to be ruled out are pigment incontinence and Warburg syndrome, among others.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">The first mutation found in the <span class="elsevierStyleItalic">CTNNB1</span> gene associated to intellectual disability was reported in a study on the autism spectrum<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and up until 2017, 20 <span class="elsevierStyleItalic">CTNNB1</span> loss-of-function mutations had been reported in 21 patients.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Even recently it was reported that <span class="elsevierStyleItalic">CTNNB1</span> gene mutations can lead to familial exudative vitreoretinopathy (FEVR) with or without extraocular manifestations.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The clinical findings identified in international literature regarding <span class="elsevierStyleBold">Neurodevelopmental Disorder with spastic diplegia and visual defects</span> (32 patients in total), including the article that collects the most patients described with this haploinsufficiency so far (16 individuals of diverse geographical origins, none Latin),<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> are listed in descending frequency order<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,8–10</span></a>:<elsevierMultimedia ident="tbl0005"></elsevierMultimedia></p><p id="par0090" class="elsevierStylePara elsevierViewall">The most significantly different characteristic in our reported case is that approximately 75% of patients with loss-of-function <span class="elsevierStyleItalic">CTNNB1</span> gene mutations have mild visual defects, mostly characterized by hyperopia or strabismus. There is an associated case report in China; however, fetal vasculature persistence has not been described in humans with loss-of-function <span class="elsevierStyleItalic">CTNNB1</span>gene mutations yet, which could be added to the list of associated ophthalmic diseases.</p><p id="par0095" class="elsevierStylePara elsevierViewall">In conclusion, this is a case of severe bilateral primary vitreous hyperplasia. The diagnosis was made based on bilateral leukocoria, ultrasound findings, and brain MRI with hyperintense vitreous on T2. As suggested by the literature, this bilateral form associated to other systemic findings was genetically studied, thus finding the first reported Colombian patient with a de novo mutation (deletion) in the <span class="elsevierStyleItalic">CTNNB1</span> gene, that also presents an ocular phenotype not previously reported.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflict of interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">No conflicts of interests have been declared by the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1655413" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1471442" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1655414" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1471443" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinical case" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflict of interest" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-08-06" "fechaAceptado" => "2020-11-25" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1471442" "palabras" => array:6 [ 0 => "<span class="elsevierStyleItalic">CTNNB1</span> gene" 1 => "Microphthalmia" 2 => "Microcephaly" 3 => "Persistent fetal vasculature" 4 => "Persistence hyperplastic primary vitreous" 5 => "Developmental disabilities" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1471443" "palabras" => array:6 [ 0 => "Gen <span class="elsevierStyleItalic">CTNNB1</span>" 1 => "Microftalmia" 2 => "Microcefalia" 3 => "Vasculatura fetal persistente" 4 => "Vítreo primario hiperplásico persistente" 5 => "Discapacidades del desarrollo" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The most cases of persistence hyperplastic primary vitreous (PHPV) are unilateral and sporadic, however, bilateral presentation could be present in a small number of patients, in whom other genetic diseases must be ruled out. We describe a case of a 2 months child with bilateral persistence hyperplastic primary vitreous confirmed by ultrasound. In addition, with neurodevelopmental defects, microcephaly, facial dimorphism, axial hypotonia, and without brain abnormalities on MRI, in whom a de novo mutation of the <span class="elsevierStyleItalic">CTNNB1</span> gene was found during the genetic study, which explains the findings.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La mayoría de los casos de persistencia de la vasculatura fetal (PVF) o persistencia del vitreo primario hiperplásico (PVPH) son de naturaleza unilateral y esporádica, sin embargo, podría tener presentación bilateral en un pequeño número de pacientes, en los cuales deben descartarse enfermedades genéticas. Describimos un caso de un lactante de 2 meses en quien se observó hiperplasia del vitreo primario bilateral confirmada por ecografía. Además, cursaba con defectos del neurodesarrollo, microcefalia, dimorfismo facial, hipotonía axial, sin alteraciones cerebrales en resonancia magnética. En el estudio genético se encontró mutación de novo del gen <span class="elsevierStyleItalic">CTNNB1</span>, que explica los hallazgos.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Zuluaga Gómez LM, Caballero Mojica SC, Vélez Rengifo GJ, Bravo Acosta JD, Montoya Villada JH. Mutación del gen <span class="elsevierStyleItalic">CTNNB1</span> asociada a alteración del neurodesarrollo, microcefalia y persistencia del vítreo primario hiperplásico bilateral: reporte de un caso y revisión de la literatura. Arch Soc Esp Oftalmol. 2022;97:44–47.</p>" ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 666 "Ancho" => 1340 "Tamanyo" => 84426 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Ocular ultrasound with a 10 MHz transducer (compact touch equipment). <span class="elsevierStyleBold">A) Right eye</span>: vitreous cavity with multiple opacities of variable reflectivity, mostly high. Axial length: 14.17 mm. no intraocular masses were found. <span class="elsevierStyleBold">B) Left eye</span>: low reflectivity image anteriorly exiting the optic nerve. Axial length: 16.14 mm. No intraocular masses were found. Concept: Right eye retinal detachment, microphthalmos and hyperplastic primary vitreous persistence in both eyes.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 604 "Ancho" => 1340 "Tamanyo" => 80762 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Examination under general anesthesia. <span class="elsevierStyleBold">A) Right eye</span>: No conjunctival or ciliary congestion, cornea with mild opacity, atalamia, iridocrystalline diaphragm completely displaced forward, iris with transillumination areas, total retrolental opacity. <span class="elsevierStyleBold">B) Left eye</span>: total retinal open funnel detachment, with tractional bands and presence of coagulated hemorrhages, without evidence of mass or exudation.</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 774 "Ancho" => 1340 "Tamanyo" => 86744 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">T1 and T2 axial MRI: right eye microphthalmia, atrophic nerve changes with retinal detachment and hyaloid canal persistence, without masses, in the left eye. The rest of brain structures are normal.</p>" ] ] 3 => array:5 [ "identificador" => "tbl0005" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => false "mostrarDisplay" => true "tabla" => array:1 [ "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="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical finding \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Description \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hypotonia and delayed motor development \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Present from early childhood. While trunk hypotonia was maintained, distal hypertonia (arms and legs) with spasticity was developed in most patients. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Speech deficiency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Varies in reports, from mild delay to no word development. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Primary or postnatal microcephaly \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Present in most (between −2.2 and −4.8 standard deviation). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Facial dimorphism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Wide nasal tip with small nostrils, long or flat filtrum and thin upper lip vermilion. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Eye disorders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Most present strabismus, hyperopia or myopia.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">There is a report of familial exudative vitreoretinopathy associated to a <span class="elsevierStyleItalic">CTNNB1</span> gene mutation and other syndromic clinical findings.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Behavioral disturbances \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Range from autism spectrum to aggressiveness and self-harm. Sleep disorders were also described in some patients. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2817899.png" ] ] ] ] ] ] "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" => "Developmental regression of hyaloid vasculature is triggered by neurons" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Yoshikawa" 1 => "T. Yamada" 2 => "I. Tai-Nagara" 3 => "K. Okabe" 4 => "Y. Kitagaw" 5 => "M. Ema" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1084/jem.20151966" "Revista" => array:5 [ "tituloSerie" => "JEM." "fecha" => "2016" "volumen" => "213" "paginaInicial" => "1175" "paginaFinal" => "1183" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Wnt signaling pathway in retinal vascularization" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "K.A. Drenser" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/EB.S94452" "Revista" => array:6 [ "tituloSerie" => "Eye Brain." 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