Letter to the Editor
Rubinstein-Taybi Syndrome: A Female Patient with a De Novo Reciprocal Translocation T(2; 16)(Q36.3; P13.3) and Dysgranulopoiesis
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Sugayama" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Leuridan Cavalcante" "apellidos" => "Torres" "email" => array:1 [ 0 => "ltorres@usp.br" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">I</span>" "identificador" => "af1-cln_65p107" ] ] ] 1 => array:3 [ "nombre" => "Maria" "apellidos" => "de Lourdes Lopes Chauffaille" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">II</span>" "identificador" => "af2-cln_65p107" ] ] ] 2 => array:3 [ "nombre" => "Thomaz Pileggi" "apellidos" => "Delboni" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">I</span>" "identificador" => "af1-cln_65p107" ] ] ] 3 => array:3 [ "nombre" => "Thelma Suely" "apellidos" => "Okay" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">I</span>" "identificador" => "af1-cln_65p107" ] ] ] 4 => array:3 [ "nombre" => "Magda" "apellidos" => "Carneiro-Sampaio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">I</span>" "identificador" => "af1-cln_65p107" ] ] ] 5 => array:3 [ "nombre" => "Sofia" "apellidos" => "Sugayama" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">I</span>" "identificador" => "af1-cln_65p107" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Pediatrics, Hospital das Clinicas, Faculdade de Medicina da Universidade de São Paulo - São Paulo/SP, Brazil" "etiqueta" => "I" "identificador" => "af1-cln_65p107" ] 1 => array:3 [ "entidad" => "Department of Hematology, Universidade Federal de São Paulo (UNIFESP) - São Paulo/SP, Brazil" "etiqueta" => "II" "identificador" => "af2-cln_65p107" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f1-cln_65p107" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 768 "Ancho" => 577 "Tamanyo" => 48317 ] ] "descripcion" => array:1 [ "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">A patient with the facial dysmorphisms typical of RTS</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Rubinstein-Taybi syndrome (RTS) is a rare developmental disorder characterized by craniofacial dysmorphisms, broad thumbs and toes as well as mental and statural deficiencies.<a class="elsevierStyleCrossRef" href="#bib1">1</a> RTS has a prevalence of 1 in 330,000 births<a class="elsevierStyleCrossRef" href="#bib2">2</a> and usually occurs sporadically, although it can be inherited as an autosomal dominant disorder.<a class="elsevierStyleCrossRefs" href="#bib2">2,4</a> The diagnosis is based on characteristic features.<a class="elsevierStyleCrossRef" href="#bib3">3</a> The main clinical symptoms are failure to thrive, cardiac defects and recurrent respiratory infections.<a class="elsevierStyleCrossRef" href="#bib4">4</a> Other variable findings are colobomas, cataracts, renal anormalities<a class="elsevierStyleCrossRefs" href="#bib3">3,4</a> and oro-dental anomalies.<a class="elsevierStyleCrossRef" href="#bib5">5</a> RTS patients also have an increased risk of developing neoplasias.<a class="elsevierStyleCrossRefs" href="#bib6">6,7</a> Several tumors have been reported in RTS patients, including meningiomas, rhabdomyosarcomas, neuroblastomas, oligodendromas, seminomas, choristomas and leukemias.<a class="elsevierStyleCrossRefs" href="#bib6">6,7</a></p><p id="para20" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">CREBBP</span> and <span class="elsevierStyleItalic">EP300</span> are the only genes associated with RTS.<a class="elsevierStyleCrossRefs" href="#bib8">8,11</a> Microdeletions at band 16p13.3 occur in 10%–25% of RTS patients.<a class="elsevierStyleCrossRef" href="#bib9">9</a> Sequence analyses have detected <span class="elsevierStyleItalic">CREBBP</span> mutations in another 56% of affected individuals. Schorry et al. (2008)<a class="elsevierStyleCrossRef" href="#bib8">8</a> evaluated genotype-phenotype correlations in 93 RTS patients and performed complete sequencing of all 31 coding regions of the <span class="elsevierStyleItalic">CREBBP</span> gene. The authors concluded that there were no statistically significant differences in the classic dysmorphic findings of RTS patients (e.g., typical facial aspects and broad thumbs and toes) with and without <span class="elsevierStyleItalic">CREBBP</span> mutations. Mutations in <span class="elsevierStyleItalic">EP300</span> have been identified in 3% of RTS patients.<a class="elsevierStyleCrossRefs" href="#bib7">7,9</a></p><p id="para30" class="elsevierStylePara elsevierViewall">RTS typically occurs as a de novo mutation in a family.<a class="elsevierStyleCrossRef" href="#bib2">2</a> Most individuals represent simplex cases (i.e., the only affected member in a family); in most instances, the parents of an individual with RTS are not affected.<a class="elsevierStyleCrossRefs" href="#bib2">2,4</a> In this case, the empiric recurrence risk for siblings is approximately 0.1%. Although individuals with RTS rarely reproduce, the theoretical risk for the offspring is 50%.<a class="elsevierStyleCrossRef" href="#bib2">2</a> Prenatal testing for at-risk pregnancies is possible if the disease-causing CREBBP mutation or deletion in the family is known.<a class="elsevierStyleCrossRef" href="#bib7">7</a></p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">CASE DESCRIPTION</span><p id="para40" class="elsevierStylePara elsevierViewall">The propositus, a 23-year-old Brazilian female patient, is the third child of healthy, non-consanguineous parents. The infant was born pre-term by Cesarean section. The birth weight was 1,900 g, the length was 47 cm, the occipitofrontal circumference (OFC) was 36 cm, and the body mass index was 31.35 (mild obesity). Developmental milestones were delayed: she sat without support at the age of 1, walked at 2.5 years and acquired control of the bowels at age 4. She spoke only a few meaningful words at the age of eighteen. The clinical history of the infancy and childhood was noteworthy, with feeding problems and recurrent respiratory infections (sinusitis, otitis medias, tonsillitis and pneumonias) from two months of age until the age of five. Splenomegaly was observed at 21 years of age, and a detailed immunological analysis of this patient was performed by Torres (2008)<a class="elsevierStyleCrossRef" href="#bib13">13</a>. Persistent mild to moderate leukocytosis (13,000 to 26,000/mm<span class="elsevierStyleSup">3</span>) was observed despite the absence of clinical signs of infection. Forty to fifty percent of blood neutrophils presented with scarce or absent granules. A myelogram also showed dysgranulopoietic granulocytes.</p><p id="cpt10" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="t1-cln_65p107"></elsevierMultimedia></p><p id="para50" class="elsevierStylePara elsevierViewall">A physical examination at 23 years of age showed a weight of 61 kg (75<a class="elsevierStyleCrossRef" href="#f1-cln_65p107">Figure 1</a>). She also had broad, radially deviated thumbs and broad halluces (<a class="elsevierStyleCrossRef" href="#f2-cln_65p107">Figure 2</a>).</p><elsevierMultimedia ident="f1-cln_65p107"></elsevierMultimedia><elsevierMultimedia ident="f2-cln_65p107"></elsevierMultimedia><p id="para60" class="elsevierStylePara elsevierViewall">Chromosome preparations were obtained from peripheral blood lymphocytes from the propositus and her parents. Karyotyping with GTG banding was performed at the 450–550 band level using standard methods<a class="elsevierStyleCrossRef" href="#bib9">9</a> by the Fleury Laboratory. The patient’s karyotype showed a balanced reciprocal translocation between chromosomes 2 and 16 without visible deletion; the full karyotype is 46, XX, t(2;16) (q36.3; p13.3) (<a class="elsevierStyleCrossRef" href="#f3-cln_65p107">Figure 3</a>). The parent’s karyotypes were normal, so this translocation was <span class="elsevierStyleItalic">de novo</span>. The recurrence risk for the parents is very low (approximately 0.1%).</p><elsevierMultimedia ident="f3-cln_65p107"></elsevierMultimedia></span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">DISCUSSION</span><p id="para70" class="elsevierStylePara elsevierViewall">Chromosomal rearrangements involving band 16p13.3 form the minority (0.6%) of <span class="elsevierStyleItalic">CREBBP</span> mutations.<a class="elsevierStyleCrossRef" href="#bib18">18</a> There have been seven reported cases of chromosomal rearrangements in RTS patients, and four of these were translocations.<a class="elsevierStyleCrossRef" href="#bib14">14</a>–<a class="elsevierStyleCrossRef" href="#bib18">18</a></p><p id="para80" class="elsevierStylePara elsevierViewall">The 4-year-old RTS boy described by Petrij et al. (1995)<a class="elsevierStyleCrossRef" href="#bib17">17</a> presented with the same translocation (2; 16) with the same breakpoints as our patient. The common clinical findings of this boy and our patient were feeding problems, short stature and recurrent respiratory infections. To the best of our knowledge, our RTS patient is the third reported case with a <span class="elsevierStyleItalic">de novo</span> reciprocal t (2;16) (q36.3; p13.3).</p><p id="para90" class="elsevierStylePara elsevierViewall">We found no other studies describing RTS patients with dysgranulopoietic neutrophils. As RTS patients have an increased risk of hematological malignancies,<a class="elsevierStyleCrossRef" href="#bib6">6</a> appropriate laboratory testing and hematological follow-up are warranted.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "cesec10" "titulo" => "INTRODUCTION" ] 1 => array:2 [ "identificador" => "cesec20" "titulo" => "CASE DESCRIPTION" ] 2 => array:2 [ "identificador" => "cesec30" "titulo" => "DISCUSSION" ] 3 => array:1 [ "titulo" => "REFERENCES" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "f1-cln_65p107" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 768 "Ancho" => 577 "Tamanyo" => 48317 ] ] "descripcion" => array:1 [ "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">A patient with the facial dysmorphisms typical of RTS</p>" ] ] 1 => array:7 [ "identificador" => "f2-cln_65p107" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 401 "Ancho" => 534 "Tamanyo" => 35827 ] ] "descripcion" => array:1 [ "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Broad and radially deviated thumbs</p>" ] ] 2 => array:7 [ "identificador" => "f3-cln_65p107" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 387 "Ancho" => 511 "Tamanyo" => 9087 ] ] "descripcion" => array:1 [ "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">GTG banding karyotype</p>" ] ] 3 => array:7 [ "identificador" => "t1-cln_65p107" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => false "mostrarDisplay" => true "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "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="middle" scope="col">Karyotype \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="left" valign="middle" scope="col">References \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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">46, XX, t(2; 16) (p13.3; p13.3) \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="top">Imaizumi, Kuroki (1991)<a class="elsevierStyleCrossRef" href="#bib15">15</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">46, XY, t(7; 16) (q34; p13.3) \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="top">Tommerup et al. (1992) <a class="elsevierStyleCrossRef" href="#bib16">16</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">46, XY, t(2; 16) (q36.3; p13.3) \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="top">Petrij et al. (1995)<a class="elsevierStyleCrossRef" href="#bib17">17</a>; Giles et al. (1997) <a class="elsevierStyleCrossRef" href="#bib19">19</a>; Petrij et al. (2000) <a class="elsevierStyleCrossRef" href="#bib20">20</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top" style="border-bottom: 2px solid black">46, XY, t(1; 16) (p34.1; p13.2) \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="top" style="border-bottom: 2px solid black">Wallerstein et al. (1997)<a class="elsevierStyleCrossRef" href="#bib21">21</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">Reciprocal translocations in RTS patients</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec10" "bibliografiaReferencia" => array:21 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Broad thumbs-hallux (Rubinstein-Taybi) Syndrome 1957–1988" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => """ JH Rubinstein \n \t\t\t\t\t\t\t\t """ ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Am J Med Genet Supplement" "fecha" => "1990" "volumen" => "6" "paginaInicial" => "3" "paginaFinal" => "16" ] ] ] ] ] ] 1 => array:3 [ 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|---|---|---|---|
| 2024 November | 2 | 0 | 2 |
| 2024 October | 30 | 18 | 48 |
| 2024 September | 38 | 15 | 53 |
| 2024 August | 41 | 14 | 55 |
| 2024 July | 22 | 17 | 39 |
| 2024 June | 27 | 16 | 43 |
| 2024 May | 35 | 12 | 47 |
| 2024 April | 22 | 8 | 30 |
| 2024 March | 35 | 15 | 50 |
| 2024 February | 23 | 12 | 35 |
| 2024 January | 17 | 10 | 27 |
| 2023 December | 12 | 14 | 26 |
| 2023 November | 13 | 14 | 27 |
| 2023 October | 29 | 21 | 50 |
| 2023 September | 19 | 17 | 36 |
| 2023 August | 7 | 8 | 15 |
| 2023 July | 13 | 13 | 26 |
| 2023 June | 9 | 1 | 10 |
| 2023 May | 3 | 0 | 3 |
| 2023 April | 2 | 0 | 2 |
| 2023 March | 5 | 1 | 6 |
| 2023 January | 2 | 1 | 3 |
| 2022 December | 8 | 2 | 10 |
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