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Flores-Terry, A. Alegre-Sánchez, P. Boixeda, J.C. López-Gutiérrez" "autores" => array:4 [ 0 => array:4 [ "nombre" => "M.Á." "apellidos" => "Flores-Terry" "email" => array:1 [ 0 => "miguelterry85@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" => "Alegre-Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "P." "apellidos" => "Boixeda" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "J.C." "apellidos" => "López-Gutiérrez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología Médico-Quirúrgica y Venereología, Hospital General Universitario de Ciudad Real, Ciudad Real, España" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Dermatología Médico-Quirúrgica y Venereología, Hospital Ramón y Cajal, Madrid, España" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Cirugía Pediátrica, Hospital Infantil La Paz, Madrid, España" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Complejo de esclerosis tuberosa asociado a hemihipertrofia y malformaciones vasculares combinadas" ] ] "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" => 1606 "Ancho" => 2336 "Tamanyo" => 253375 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Limb asymmetry with overgrowth of the left arm. B and C, Capillary and venous vascular malformations on the anterior and posterior aspects of the arm.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Tuberous sclerosis complex (TSC), an autosomal dominant disorder with variable expressivity, is caused by mutations in the tumor suppressor genes <span class="elsevierStyleItalic">TSC1</span> and <span class="elsevierStyleItalic">TSC2</span>, which encode hamartin and tuberin proteins, respectively.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–3</span></a> TSC manifests with the formation of hamartomas in multiple organs, mainly the skin, central nervous system, kidneys, lungs, and heart.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–3</span></a> Vascular anomalies associated with overgrowth, hypertrophy, or gigantism are uncommon in TSC.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> We report the case of a TSC patient with congenital hypertrophy and combined vascular malformations of the left arm.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A 17-year-old adolescent girl, who was diagnosed with TSC at 9 years of age, was followed from birth for hypertrophy and combined vascular malformations of the left arm. The diagnosis of TSC was confirmed upon identification of the c.235G>T mutation in <span class="elsevierStyleItalic">TSC2</span> in heterozygosis, in the absence of any clinical signs of the disease. The patient's mother carried the same mutation and presented clinical signs of TSC. A physical examination carried out during the first months of life revealed telangiectatic and purpuric vascular lesions (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A) accompanied by multiple visible capillaries and venous vessels (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B and C) on the left arm, the diameter of which was enlarged. No skin lesions indicative of TSC were observed. Doppler ultrasound performed at 20 days of age revealed no alterations of the arterial or deep venous systems. At 4 months of age, a deep skin biopsy, which included muscle, showed enlargement of the blood vessels in the dermis and subcutaneous tissue suggestive of capillary and venous malformations, in addition to ectasia of the lymphatic vessels. Immunohistochemistry revealed positive staining for D2-40 and negative staining for GLUT1 and WT1. No alterations in muscle tissue were observed, and atypia and mitotic figures were absent. Hypopigmented macules on the thighs, facial angiofibromas (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), and periungual fibromas on the hands and feet became more evident once the patient reached 8 years of age, and were accompanied by Shagreen patches on the trunk that were compatible with TSC, which was confirmed by genetic study. A general physical examination and imaging techniques including conventional radiology, abdominal and pelvic ultrasound, brain magnetic resonance imaging, and cardiac ultrasound revealed no systemic alterations. The patient was diagnosed with predominantly lymphatic combined vascular malformation associated with TSC caused by <span class="elsevierStyleItalic">TSC2</span> mutation. At age 11 years the patient began treatment with oral rapamycin (0.8 mg/m<span class="elsevierStyleSup">2</span>/12 h) for 6 months. Because no decrease in the circumference of the affected arm was observed and the patient showed no systemic signs, rapamycin treatment was discontinued. Since the age of 14 years the patient's superficial capillary malformations have been treated with pulsed dye laser (PDL) (10<span class="elsevierStyleHsp" style=""></span>mm, 10<span class="elsevierStyleHsp" style=""></span>ms, 6<span class="elsevierStyleHsp" style=""></span>J/cm<span class="elsevierStyleSup">2</span>), and the superficial venous malformations have been treated with multiplex neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (PDL [10<span class="elsevierStyleHsp" style=""></span>mm, 10<span class="elsevierStyleHsp" style=""></span>ms, 6<span class="elsevierStyleHsp" style=""></span>J/ cm<span class="elsevierStyleSup">2</span>] followed after a 1-s delay by Nd:YAG laser [10<span class="elsevierStyleHsp" style=""></span>mm, 15<span class="elsevierStyleHsp" style=""></span>ms, 70<span class="elsevierStyleHsp" style=""></span>J/cm<span class="elsevierStyleSup">2</span>]) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>A and B).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The phosphatidylinositol 3-kinase (PI3K/AKT)/phosphatase and tensin homolog(PTEN)/mammalian target of rapamycin (mTOR) pathway is implicated in the pathogenesis of hamartomatous syndromes such as TSC, vascular anomalies, overgrowth, and malignant tumors.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,4–6</span></a> mTOR, a kinase belonging to the phosphatidyl-3-inositol family, consists of 2 multiprotein complexes (mammalian target of rapamycin complex [mTORC]1 and mTORC2) and is involved in the regulation of multiple processes associated with growth, cell differentiation, angiogenesis, and modulation of the inflammatory response.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> The angiogenic activity of mTOR is mediated primarily via the translation and activation of hypoxia-inducible factor 1 (HIF-1), which in turn is implicated in VEGF expression in situations of cellular hypoxia and suppresses mTORC1 activity.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> The fact that TSC is one of the diseases most clearly associated with dysregulation of the mTOR pathway explains the appearance of different types of vascular malformations in this disease, although these alterations are rarely reported.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Vascular anomalies described in TSC include angiomyolipomas, lymphatic malformations, and, less commonly, arterial anomalies (occlusion, stenosis, aneurysms), which are likely related to alterations of the vasa vasorum caused by hamartomas.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Lymphedema in TSC<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> may be the result of lymphatic malformations. It has been proposed that congenital and acquired lymphedema are more frequent in TSC.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The involvement of an entire body segment, as in the present case, may be due to the loss of heterozygosity during early fetal development,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> combined with the germinal mutation. Postzygotic mosaic mutations that affect cell signaling pathways regulating cell growth, apoptosis, or migration can give rise to regional alterations, in some cases accompanied by overgrowth, which can compromise the skin, subcutaneous tissue, muscle, bone, and/or nerves. In terms of severity, overgrowth can be variable, stable, or progressive.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> When monitoring these patients, it should be borne in mind that alterations in these pathways can also increase the likelihood of developing various malignant tumors.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">In TSC patients, mTOR inhibitors such as rapamycin (sirolimus) have shown beneficial effects on neurological signs, but no clear effects on overgrowth and/or vascular malformations.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Good results have been reported in other patients with vascular malformations.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> Further studies with better dose control and longer periods of administration are likely needed to determine its true efficacy. Blockade of the mTOR pathway could play a fundamental role in the development of vascular lesions in TSC patients.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0030" 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: Flores-Terry MÁ, Alegre-Sánchez A, Boixeda P, López-Gutiérrez JC. Complejo de esclerosis tuberosa asociado a hemihipertrofia y malformaciones vasculares combinadas. Actas Dermosifiliogr. 2019;110:164–167.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1606 "Ancho" => 2336 "Tamanyo" => 253375 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Limb asymmetry with overgrowth of the left arm. B and C, Capillary and venous vascular malformations on the anterior and posterior aspects of the arm.</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" => 1032 "Ancho" => 850 "Tamanyo" => 100067 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Tuberous sclerosis complex patient with multiple facial angiofibromas.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1362 "Ancho" => 2336 "Tamanyo" => 310063 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Patient at 16 years of age, before (A) and after (B) treatment of capillary and venous malformations with pulsed dye laser and multiplex neodymium-doped yttrium aluminum garnet (Nd:YAG) laser, respectively.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tuberous sclerosis complex: an update for dermatologists" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S.K. 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año/Mes | Html | Total | |
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2024 Noviembre | 6 | 15 | 21 |
2024 Octubre | 98 | 60 | 158 |
2024 Septiembre | 92 | 46 | 138 |
2024 Agosto | 117 | 65 | 182 |
2024 Julio | 106 | 50 | 156 |
2024 Junio | 123 | 60 | 183 |
2024 Mayo | 95 | 42 | 137 |
2024 Abril | 93 | 46 | 139 |
2024 Marzo | 120 | 58 | 178 |
2024 Febrero | 105 | 61 | 166 |
2024 Enero | 114 | 46 | 160 |
2023 Diciembre | 101 | 29 | 130 |
2023 Noviembre | 120 | 34 | 154 |
2023 Octubre | 119 | 48 | 167 |
2023 Septiembre | 100 | 35 | 135 |
2023 Agosto | 72 | 22 | 94 |
2023 Julio | 103 | 39 | 142 |
2023 Junio | 54 | 23 | 77 |
2023 Mayo | 127 | 23 | 150 |
2023 Abril | 114 | 21 | 135 |
2023 Marzo | 174 | 19 | 193 |
2023 Febrero | 162 | 26 | 188 |
2023 Enero | 133 | 28 | 161 |
2022 Diciembre | 109 | 32 | 141 |
2022 Noviembre | 123 | 28 | 151 |
2022 Octubre | 104 | 30 | 134 |
2022 Septiembre | 106 | 36 | 142 |
2022 Agosto | 93 | 44 | 137 |
2022 Julio | 65 | 45 | 110 |
2022 Junio | 56 | 31 | 87 |
2022 Mayo | 119 | 52 | 171 |
2022 Abril | 122 | 33 | 155 |
2022 Marzo | 147 | 70 | 217 |
2022 Febrero | 151 | 37 | 188 |
2022 Enero | 184 | 38 | 222 |
2021 Diciembre | 159 | 44 | 203 |
2021 Noviembre | 126 | 45 | 171 |
2021 Octubre | 188 | 55 | 243 |
2021 Septiembre | 130 | 39 | 169 |
2021 Agosto | 137 | 35 | 172 |
2021 Julio | 121 | 25 | 146 |
2021 Junio | 142 | 37 | 179 |
2021 Mayo | 236 | 44 | 280 |
2021 Abril | 189 | 86 | 275 |
2021 Marzo | 74 | 23 | 97 |
2021 Febrero | 72 | 32 | 104 |
2021 Enero | 47 | 16 | 63 |
2020 Diciembre | 44 | 13 | 57 |
2020 Noviembre | 35 | 19 | 54 |
2020 Octubre | 33 | 18 | 51 |
2020 Septiembre | 32 | 11 | 43 |
2020 Agosto | 15 | 25 | 40 |
2020 Julio | 21 | 7 | 28 |
2020 Junio | 25 | 24 | 49 |
2020 Mayo | 20 | 15 | 35 |
2020 Abril | 20 | 15 | 35 |
2020 Marzo | 19 | 5 | 24 |
2020 Febrero | 3 | 0 | 3 |
2019 Mayo | 1 | 0 | 1 |