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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Magnetic resonance imaging of the brain of one of the patient&#8217;s daughters showing a popcorn-like image compatible with cerebral cavernous malformation&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Medical History</span><p id="par0005" class="elsevierStylePara elsevierViewall">A 69-year-old man presented for evaluation of skin lesions on the chest that had appeared several years earlier and had grown progressively&#46; He had no medical history of interest&#46; His family history included a daughter who had experienced a spontaneous brain hemorrhage and another daughter with venous malformations of the spine&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Physical Examination</span><p id="par0010" class="elsevierStylePara elsevierViewall">Examination revealed grouped violaceous papules on the presternal region and the face&#44; including the lips and oral mucosa &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Deeper&#44; larger lesions were also observed on the arms&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Histopathology</span><p id="par0015" class="elsevierStylePara elsevierViewall">A skin biopsy showed dilated vascular lumina and negative WT-1 and D2-40 staining&#44; findings compatible with a venous malformation &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Additional Tests</span><p id="par0020" class="elsevierStylePara elsevierViewall">A genetic study revealed a heterozygous pathogenic variant of the <span class="elsevierStyleItalic">KRIT1</span> gene in the patient and 4 of his children&#46; Magnetic resonance imaging &#40;MRI&#41; showed cerebral venous malformations in one of the patient&#8217;s daughters &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; None of the remaining family members who carried the mutation showed any vascular alterations of the central nervous system &#40;CNS&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">What is Your Diagnosis&#63;</span><p id="par0025" class="elsevierStylePara elsevierViewall">Diagnosis&#58; Cerebral cavernous malformation &#40;CCM&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Discussion</span><p id="par0030" class="elsevierStylePara elsevierViewall">CCM presents with venous malformations that tend to mainly affect the brain&#44; but can also affect the skin&#44; spinal cord&#44; and retina&#46; CCM most commonly affects the CNS&#44; causing neurological signs including seizures&#44; focal neurological deficits&#44; and cerebral hemorrhage in the most severe cases&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Histologically it is characterized by the formation of enlarged and irregular vascular lumina that are composed of a single layer of endothelial cells and lack other supporting structures&#44; such as elastic fibers and smooth muscle&#44; making them more prone to leakage and disrupting the blood&#8211;brain barrier&#46; CCM can occur sporadically or can be inherited in an autosomal dominant manner&#44; with variable expression and incomplete clinical and radiological penetrance&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Genetic analysis of this condition is positive in 70&#37; of cases&#44; revealing mutations that cause loss of function of a protein encoded at 3 different loci&#44; in the following order of frequency&#58; <span class="elsevierStyleItalic">CCM1</span>&#47;<span class="elsevierStyleItalic">KRIT1</span> &#40;7q11-q22&#41;&#59; <span class="elsevierStyleItalic">CCM2</span>&#47;Malcaverin &#40;7p13-15&#41;&#59; and <span class="elsevierStyleItalic">CCM3</span>&#47;<span class="elsevierStyleItalic">PDCD10</span> &#40;3q25&#46;2q27&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Screening for nervous system involvement is performed using gradient echo MRI&#46; MRI reveals a characteristic popcorn-like appearance&#44; consisting of a well-delimited reticulated nucleus&#44; heterogeneous signal due to bleeding at different stages&#44; and a hypointense hemosiderin ring&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> To date&#44; surgery is the only described treatment&#44; and is indicated for single&#44; symptomatic lesions in specific locations&#44; but not for multiple or asymptomatic lesions&#44; with certain exceptions&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Long-term use of statins is being studied in a clinical trial&#44; for which data are not yet available&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">We describe a case in which the presence of cutaneous venous malformations in multiple individuals in the same family was crucial for early diagnosis and treatment of this disease&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Conflicts of Interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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