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&#43;1&#46;44&#41;&#44; head circumference of 50<span class="elsevierStyleHsp" style=""></span>cm &#40;<span class="elsevierStyleItalic">z</span>-score&#44; &#8722;2&#46;21&#41; and arm span of 129&#46;5<span class="elsevierStyleHsp" style=""></span>cm&#46; Target height 167&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>cm &#40;<span class="elsevierStyleItalic">z</span>-score&#44; &#8722;1&#46;36&#41;&#46; Ptosis&#44; epicanthal folds&#44; upslanting palpebral fissures&#44; broad nasal bridge&#44; prominent ears&#44; prognathism&#44; multiple dental cavities&#44; microcephaly and low anterior hairline&#46; Bilateral limited forearm pronosupination with inability to get past the neutral position&#46; Shortening of fifth metacarpal&#46; Genu valgus&#44; flat feet with superimposition of the fifth toe&#46; Normal heart and lung sounds on auscultation&#46; Tanner I &#40;G1&#44; P1&#44; Aa&#41;&#44; testicular volume of 1<span class="elsevierStyleHsp" style=""></span>mL&#44; penis measuring 3&#46;4<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>1&#46;4<span class="elsevierStyleHsp" style=""></span>cm &#40;<span class="elsevierStyleItalic">z</span>-score&#44; &#8722;2&#46;9&#41;&#44; absence of gynecomastia&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The findings of diagnostic tests were&#58; normal levels of thyroid hormones&#44; follicle-stimulating hormone&#44; luteinizing hormone&#44; testosterone&#44; estradiol&#44; inhibin B and anti-M&#252;llerian hormone&#46; Normal carbohydrate metabolism and lipid panel&#46; Proximal radioulnar synostosis on forearm X-ray &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; White matter lesions of a predominantly frontal location and dilatation of periventricular Virchow-Robin spaces on magnetic resonance imaging&#44; compatible with nonspecific leukoencephalopathy&#46; Karyotype mosaicism with 49&#44;XXXXY in 90&#37; of cells and 48&#44;XXXY in 10&#37; of cells&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The incidence of the 48&#44;XXXY and 49&#44;XXXXY variants is considerably lower compared to KS&#44; of 1 in 17<span class="elsevierStyleHsp" style=""></span>000 to 1 in 50<span class="elsevierStyleHsp" style=""></span>000 live births and 1 in 85<span class="elsevierStyleHsp" style=""></span>000 to 1 in 100<span class="elsevierStyleHsp" style=""></span>000 live births&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1&#44;2</span></a> We present a case of an exceedingly rare form of mosaicism&#44; 48&#44;XXXY&#47;49&#44;XXXXY&#44; whose incidence is unknown&#46; While KS is associated with high stature&#44; as does the 48&#44;XXXY variant&#44; the 49&#44;XXXXY variant presents with short stature for reasons that have yet to be established&#46; Our patient had normal stature&#44; although his height was high relative to his target height&#46; Most of the features described above are shared by both variants and 47&#44;XXY variant<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The frequency of radioulnar synostosis increases with increasing number of X chromosomes&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> Thus&#44; although these features have been described in 47&#44;XXY&#47;46&#44;XX mosaicism&#44; they are more frequent in variants with tetrasomy and pentasomy&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> Other congenital malformations&#44; such as cleft palate&#44; kidney or hip dysplasia or inguinal hernia&#44; were not present in our patient&#44; despite their increased prevalence and severity in individuals with the 49&#44;XXXXY variant&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1&#44;4</span></a> Hypogonadism may manifest with micropenis&#44; cryptorchidism&#44; scrotal hypoplasia or hypergonadotropic hypogonadism&#46; The latter is a feature shared with KS and its variants&#46; In the prepubertal stage&#44; our patient had a testicular volume of 1<span class="elsevierStyleHsp" style=""></span>mL and micropenis&#44; which are also common findings in all variants&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> The 47&#44;XXY and the tetrasomy and pentasomy variants manifest with a broad spectrum of cognitive impairment&#44; with the most severe impairment found in association with the 49&#44;XXXXY variant<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1&#44;4</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Our patient had severe psychomotor impairment with significant deficits in expressive language&#44; which is a common feature of all variants&#46; Tartaglia et al&#46; described the presence of motor delays and hypotonia in 100&#37; of 49&#44;XXXXY individuals&#44; with development of independent ambulation at a mean age of 25&#46;5 months&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> Visootsak et al&#46; estimated that the intellectual quotient decreases by 10&#8211;15 points with each additional X chromosome&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">2&#44;5</span></a> Abnormalities of the brain parenchyma &#40;ventriculomegaly&#44; white matter hyperintensities&#41; and the craniocervical junction are also associated to variants of KS&#44; as described by Milani et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> With the exception of the nonspecific white matter lesions&#44; we did not find any of these abnormalities in our patient&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion&#44; karyotype 48&#44;XXXY&#47;49&#44;XXXXY is a rare sex chromosome aneuploidy that&#44; while sharing some features with KS&#44; is characterised by a higher frequency of congenital anomalies &#40;especially proximal radioulnar synostosis&#41; and cognitive and behavioural abnormalities that are generally more severe than those found in association with the 47&#44;XXY variant&#46; These patients require multidisciplinary follow-up&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; del R&#237;o RG&#44; dos Santos TJ&#44; Travieso-Su&#225;rez L&#44; Mu&#241;oz Calvo MT&#44; Argente J&#46; Cariotipo 48&#44;XXXY&#47;49&#44;XXXXY y sin&#243;stosis radioulnar proximal&#46; An Pediatr &#40;Barc&#41;&#46; 2018&#59;88&#58;282&#8211;284&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#40;A and B&#41; Frontal and lateral view of the patient&#46; &#40;C&#41; Forearm A-ray revealing radioulnar synostosis&#46;</p>"
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          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">IQ&#44; intellectual quotient&#46;</p>"
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                  <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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Karyotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">47&#44;XXY &#40;SK&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">48&#44;XXXY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">49&#44;XXXXY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient &#40;49&#44;XXXXY&#47;48&#44;XXXY&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prevalence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#58;650&#8211;1&#58;1000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#58;17<span class="elsevierStyleHsp" style=""></span>000&#8211;1&#58;45<span class="elsevierStyleHsp" style=""></span>000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#58;85<span class="elsevierStyleHsp" style=""></span>000&#8211;1&#58; 100<span class="elsevierStyleHsp" style=""></span>000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age at diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;5&#37; before age 10 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;70&#37; before age 10 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mean age at diagnosis&#58; 4 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Age 4 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High stature&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High stature&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Low stature &#40;limited data&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High stature &#40;75th percentile with target height at 10th percentile&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Round face&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mild facial dysmorphism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Round face&#44; facial asymmetries&#44; epicanthal folds&#44; upslanting palpebral fissures&#44; orbital hypertelorism&#44; broad nasal bridge&#44; micrognathia&#44; narrow shoulders&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Round face&#44; ptosis&#44; epicanthal folds&#44; upslanting palpebral fissures&#44; microcephaly&#44; low hairline&#44; dental&#44; prognathism&#44; narrow shoulders&#44; micropenis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Congenital malformations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clinodactyly&#44; inguinal hernia&#44; cleft palate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clinodactyly&#44; radioulnar synostosis&#44; dental problems&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Radioulnar synostosis&#44; hip dysplasia&#44; urogenital malformations&#44; cleft palate&#44; inguinal hernia&#44; clubfoot&#44; heart malformations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Radioulnar synostosis&#44; flat feet&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypergonadotropic hypogonadism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not applicable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Development and cognition&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Motor and language delay &#40;40&#8211;75&#37;&#41;&#59; mean IQ 89&#8211;102&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tremors&#44; psychomotor impairment&#59; mean IQ 70&#8211;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Motor and language delay &#40;100&#37;&#41;&#59; mean IQ 20&#8211;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Motor and language delay&#59; IQ<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics of chromosome variants 47&#44;XXY&#59; 48&#44;XXXY&#59; 49&#44;XXXXY and of the patient with 48&#44;XXXY&#47;49&#44;XXXXY mosaicism&#46;</p>"
        ]
      ]
    ]
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Scientific Letter
Karyotype 48,XXXY/49,XXXXY and proximal radioulnar synostosis
Cariotipo 48,XXXY/49,XXXXY y sinóstosis radioulnar proximal
Raquel Girón del Ríoa, Tiago Jeronimo dos Santosa, Lourdes Travieso-Suáreza, María Teresa Muñoz Calvoa,b,c,
Corresponding author
maitemunozcalvo@gmail.com

Corresponding author.
, Jesús Argentea,b,c,d
a Servicio de Endocrinología, Hospital Infantil Universitario Niño Jesús, Madrid, Spain
b Departamento de Pediatría, Universidad Autónoma de Madrid, Madrid, Spain
c CIBEROBN Instituto de Salud Carlos III, Madrid, Spain
d IMDEA Food Institute, CEIUAM+CSIC, Madrid, Spain
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The findings of history taking were&#58; term delivery &#40;38<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>2 weeks&#41; with a birth weight of 2860<span class="elsevierStyleHsp" style=""></span>g &#40;<span class="elsevierStyleItalic">z</span>-score&#44; &#8722;0&#46;71&#41;&#44; length of 47<span class="elsevierStyleHsp" style=""></span>cm &#40;<span class="elsevierStyleItalic">z</span>-score&#44; &#8722;1&#46;12&#41; and head circumference of 35<span class="elsevierStyleHsp" style=""></span>cm &#40;<span class="elsevierStyleItalic">z</span>-score&#44; &#43;0&#46;09&#41;&#46; Apgar score of 7&#47;9&#46; Normal genitals&#46; Metabolic screen and hearing test with normal results&#46; Follow-up in the cardiology department due to patent foramen oval permeable and multiple apical ventricular septal defects that resolved spontaneously&#46; Dental caries and recurrent dental abscesses&#46; Severe psychomotor impairment&#44; with an intellectual quotient of less than 50&#44; with development of smiling at 1 month of life&#44; ability to hold head at 6 months&#44; independent sitting at 2 years&#44; and independent ambulation at 3 years&#46; Scarce and repetitive speech with dyslalia&#44; greater impairment in expressive than in receptive communication&#46; Normal growth velocity maintained at the 50th&#8211;75th percentile for height and 90th&#8211;97th percentile for weight&#44; bone age delay of approximately 1 year&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The findings of physical examination were&#58; weight of 37&#46;8<span class="elsevierStyleHsp" style=""></span>kg &#40;<span class="elsevierStyleItalic">z</span>-score&#44; &#43;2&#46;77&#41;&#44; height of 136&#46;6<span class="elsevierStyleHsp" style=""></span>cm &#40;<span class="elsevierStyleItalic">z</span>-score&#44; &#43;0&#46;23&#41;&#44; BMI of 20&#46;3<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span> &#40;<span class="elsevierStyleItalic">z</span>-score&#44; &#43;1&#46;44&#41;&#44; head circumference of 50<span class="elsevierStyleHsp" style=""></span>cm &#40;<span class="elsevierStyleItalic">z</span>-score&#44; &#8722;2&#46;21&#41; and arm span of 129&#46;5<span class="elsevierStyleHsp" style=""></span>cm&#46; Target height 167&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>cm &#40;<span class="elsevierStyleItalic">z</span>-score&#44; &#8722;1&#46;36&#41;&#46; Ptosis&#44; epicanthal folds&#44; upslanting palpebral fissures&#44; broad nasal bridge&#44; prominent ears&#44; prognathism&#44; multiple dental cavities&#44; microcephaly and low anterior hairline&#46; Bilateral limited forearm pronosupination with inability to get past the neutral position&#46; Shortening of fifth metacarpal&#46; Genu valgus&#44; flat feet with superimposition of the fifth toe&#46; Normal heart and lung sounds on auscultation&#46; Tanner I &#40;G1&#44; P1&#44; Aa&#41;&#44; testicular volume of 1<span class="elsevierStyleHsp" style=""></span>mL&#44; penis measuring 3&#46;4<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>1&#46;4<span class="elsevierStyleHsp" style=""></span>cm &#40;<span class="elsevierStyleItalic">z</span>-score&#44; &#8722;2&#46;9&#41;&#44; absence of gynecomastia&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The findings of diagnostic tests were&#58; normal levels of thyroid hormones&#44; follicle-stimulating hormone&#44; luteinizing hormone&#44; testosterone&#44; estradiol&#44; inhibin B and anti-M&#252;llerian hormone&#46; Normal carbohydrate metabolism and lipid panel&#46; Proximal radioulnar synostosis on forearm X-ray &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; White matter lesions of a predominantly frontal location and dilatation of periventricular Virchow-Robin spaces on magnetic resonance imaging&#44; compatible with nonspecific leukoencephalopathy&#46; Karyotype mosaicism with 49&#44;XXXXY in 90&#37; of cells and 48&#44;XXXY in 10&#37; of cells&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The incidence of the 48&#44;XXXY and 49&#44;XXXXY variants is considerably lower compared to KS&#44; of 1 in 17<span class="elsevierStyleHsp" style=""></span>000 to 1 in 50<span class="elsevierStyleHsp" style=""></span>000 live births and 1 in 85<span class="elsevierStyleHsp" style=""></span>000 to 1 in 100<span class="elsevierStyleHsp" style=""></span>000 live births&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1&#44;2</span></a> We present a case of an exceedingly rare form of mosaicism&#44; 48&#44;XXXY&#47;49&#44;XXXXY&#44; whose incidence is unknown&#46; While KS is associated with high stature&#44; as does the 48&#44;XXXY variant&#44; the 49&#44;XXXXY variant presents with short stature for reasons that have yet to be established&#46; Our patient had normal stature&#44; although his height was high relative to his target height&#46; Most of the features described above are shared by both variants and 47&#44;XXY variant<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The frequency of radioulnar synostosis increases with increasing number of X chromosomes&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a> Thus&#44; although these features have been described in 47&#44;XXY&#47;46&#44;XX mosaicism&#44; they are more frequent in variants with tetrasomy and pentasomy&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a> Other congenital malformations&#44; such as cleft palate&#44; kidney or hip dysplasia or inguinal hernia&#44; were not present in our patient&#44; despite their increased prevalence and severity in individuals with the 49&#44;XXXXY variant&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1&#44;4</span></a> Hypogonadism may manifest with micropenis&#44; cryptorchidism&#44; scrotal hypoplasia or hypergonadotropic hypogonadism&#46; The latter is a feature shared with KS and its variants&#46; In the prepubertal stage&#44; our patient had a testicular volume of 1<span class="elsevierStyleHsp" style=""></span>mL and micropenis&#44; which are also common findings in all variants&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> The 47&#44;XXY and the tetrasomy and pentasomy variants manifest with a broad spectrum of cognitive impairment&#44; with the most severe impairment found in association with the 49&#44;XXXXY variant<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1&#44;4</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Our patient had severe psychomotor impairment with significant deficits in expressive language&#44; which is a common feature of all variants&#46; Tartaglia et al&#46; described the presence of motor delays and hypotonia in 100&#37; of 49&#44;XXXXY individuals&#44; with development of independent ambulation at a mean age of 25&#46;5 months&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a> Visootsak et al&#46; estimated that the intellectual quotient decreases by 10&#8211;15 points with each additional X chromosome&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">2&#44;5</span></a> Abnormalities of the brain parenchyma &#40;ventriculomegaly&#44; white matter hyperintensities&#41; and the craniocervical junction are also associated to variants of KS&#44; as described by Milani et al&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a> With the exception of the nonspecific white matter lesions&#44; we did not find any of these abnormalities in our patient&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">In conclusion&#44; karyotype 48&#44;XXXY&#47;49&#44;XXXXY is a rare sex chromosome aneuploidy that&#44; while sharing some features with KS&#44; is characterised by a higher frequency of congenital anomalies &#40;especially proximal radioulnar synostosis&#41; and cognitive and behavioural abnormalities that are generally more severe than those found in association with the 47&#44;XXY variant&#46; These patients require multidisciplinary follow-up&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; del R&#237;o RG&#44; dos Santos TJ&#44; Travieso-Su&#225;rez L&#44; Mu&#241;oz Calvo MT&#44; Argente J&#46; Cariotipo 48&#44;XXXY&#47;49&#44;XXXXY y sin&#243;stosis radioulnar proximal&#46; An Pediatr &#40;Barc&#41;&#46; 2018&#59;88&#58;282&#8211;284&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">&#40;A and B&#41; Frontal and lateral view of the patient&#46; &#40;C&#41; Forearm A-ray revealing radioulnar synostosis&#46;</p>"
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          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">IQ&#44; intellectual quotient&#46;</p>"
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                  <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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Karyotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">47&#44;XXY &#40;SK&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">48&#44;XXXY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">49&#44;XXXXY&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient &#40;49&#44;XXXXY&#47;48&#44;XXXY&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prevalence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#58;650&#8211;1&#58;1000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#58;17<span class="elsevierStyleHsp" style=""></span>000&#8211;1&#58;45<span class="elsevierStyleHsp" style=""></span>000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#58;85<span class="elsevierStyleHsp" style=""></span>000&#8211;1&#58; 100<span class="elsevierStyleHsp" style=""></span>000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No data&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age at diagnosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;5&#37; before age 10 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#62;70&#37; before age 10 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mean age at diagnosis&#58; 4 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Age 4 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Height&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High stature&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High stature&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Low stature &#40;limited data&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">High stature &#40;75th percentile with target height at 10th percentile&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Round face&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mild facial dysmorphism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Round face&#44; facial asymmetries&#44; epicanthal folds&#44; upslanting palpebral fissures&#44; orbital hypertelorism&#44; broad nasal bridge&#44; micrognathia&#44; narrow shoulders&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Round face&#44; ptosis&#44; epicanthal folds&#44; upslanting palpebral fissures&#44; microcephaly&#44; low hairline&#44; dental&#44; prognathism&#44; narrow shoulders&#44; micropenis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Congenital malformations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clinodactyly&#44; inguinal hernia&#44; cleft palate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clinodactyly&#44; radioulnar synostosis&#44; dental problems&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Radioulnar synostosis&#44; hip dysplasia&#44; urogenital malformations&#44; cleft palate&#44; inguinal hernia&#44; clubfoot&#44; heart malformations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Radioulnar synostosis&#44; flat feet&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypergonadotropic hypogonadism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not applicable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Development and cognition&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Motor and language delay &#40;40&#8211;75&#37;&#41;&#59; mean IQ 89&#8211;102&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Tremors&#44; psychomotor impairment&#59; mean IQ 70&#8211;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Motor and language delay &#40;100&#37;&#41;&#59; mean IQ 20&#8211;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Motor and language delay&#59; IQ<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics of chromosome variants 47&#44;XXY&#59; 48&#44;XXXY&#59; 49&#44;XXXXY and of the patient with 48&#44;XXXY&#47;49&#44;XXXXY mosaicism&#46;</p>"
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      ]
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    "bibliografia" => array:2 [
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Article information
ISSN: 23412879
Original language: English
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Idiomas
Anales de Pediatría (English Edition)
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