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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Ventilatory support modalities used &#40;bars&#41; and number of patients supported by each modality at home discharge and as of December 2015&#46;</p> <p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">NIV&#44; noninvasive ventilation with mask&#59; PNP&#44; phrenic nerve pacing&#59; TRACH&#44; tracheostomy&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Congenital central hypoventilation syndrome &#40;CCHS&#41;&#44; also known as &#8220;Ondine&#39;s curse&#8221;&#44; is a very rare genetic disorder of the autonomic nervous system &#40;ANS&#41; characterised by the loss of autonomic control of respiration&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">1&#44;2</span></a> It typically manifests during non-REM sleep or&#44; in the most severe cases&#44; throughout the sleep cycle and even during waking hours&#46; It may be associated with other ANS dysregulation disorders &#40;disturbances in the automatic control of heart rate&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">3</span></a> gastrointestinal motility and automatic eye movements&#44;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">4&#44;5</span></a> Hirschsprung disease<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a> or neural crest tumours<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">7&#44;8</span></a>&#41;&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">It is caused by heterozygous mutations in the paired-like homeobox 2B gene &#40;<span class="elsevierStyleItalic">PHOX2B</span>&#41;&#44; which plays a key role in the development of the ANS during embryogenesis&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">9&#44;10</span></a> The most frequent mutations &#40;90&#37; of cases&#41; correspond to what are known as polyalanine repeat expansion mutations &#40;PARMs&#41;&#44; which consist in expansions of the segment of 20 alanine residues located in exon 3 of <span class="elsevierStyleItalic">PHOX2B</span>&#59; these expansions have variable length&#44; and genotypes have been found with lengths ranging from 20&#47;24 to 20&#47;33&#46; The remaining 10&#37; of identified mutations are nonpolyalanine repeat expansion mutations &#40;NPARMs&#41;&#44; missense&#44; nonsense or frameshift mutations<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a> or&#44; more rarely &#40;&#60;1&#37;&#41;&#44; deletions or duplications of exon 3 or the entire gene&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a> Most cases correspond to <span class="elsevierStyleItalic">de novo</span> mutations&#44; although up to 25&#37; of asymptomatic parents may have somatic mosaicism&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">13</span></a> Genetic testing confirms the diagnosis and provides a measure of severity&#44; as mutations with shorter expansions &#40;20&#47;24 and 20&#47;25&#41; have variable penetrance and may even manifest with a normal phenotype&#44; while PARMs involving larger expansions &#40;20&#47;27 and 20&#47;33&#41; are associated with more severe ANS dysregulation and increased need for mechanical ventilation &#40;MV&#41; up to 24<span class="elsevierStyleHsp" style=""></span>h a day&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">14&#44;15</span></a> Cases due to NPARMs are associated with a higher incidence of tumours and Hirschsprung disease&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">16</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Ventilator dependence usually begins after birth &#40;early-onset CCHS&#41;&#59; although in some cases&#44; hypoventilation remains undetected or manifests at later ages&#46; Diagnosis is usually made one month after birth and in some cases at adult ages in adult carriers of mosaic or less severe mutations&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">17&#8211;20</span></a> There are other forms of primary central hypoventilation with late onset and no known associated mutation that differ from CCHS&#44; such as rapid-onset obesity with hypoventilation&#44; hypothalamic dysfunction and autonomic dysregulation &#40;ROHHAD&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">21&#44;22</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Children with CCHS require optimised MV at home to survive and&#47;or achieve optimal neurodevelopmental outcomes&#44; therefore early diagnosis and continuous monitoring of their respiratory status are key to prevent complications and sequelae secondary to hypoxaemia and hypercapnia&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">15&#44;23</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">This is a very rare disease of unknown prevalence&#44; although the latter is estimated at 1 in 200<span class="elsevierStyleHsp" style=""></span>000 live births&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">24</span></a> The European Central Hyperventilation Syndrome Consortium was constituted in 2010 with the purpose of optimising the management of these patients<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">25</span></a> &#40;<a href="http://www.ichsnetwork.eu/">www&#46;ichsnetwork&#46;eu&#47;</a>&#41;&#44; and within this framework an online European registry of patients was created&#44; that adheres to current regulations on safety&#44; anonymity and confidentiality&#46; At present&#44; fourteen European countries&#44; including Spain&#44; participate in the registry&#46; The objectives of this study were to&#58; &#40;a&#41; learn the phenotypic and genotypic characteristics&#44; clinical presentation&#44; MV approaches used and outcomes of Spanish patients with a CCHS diagnosis included in the European registry&#44; and &#40;b&#41; identify relevant aspects in the management of these patients that could be improved&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">The implementation of the European registry in Spain was authorised by the competent local Clinical Research Ethics Committee and announced through different scientific societies and the Spanish Association of CCHS patients and their families &#40;<a href="http://www.sindromedeondine.es/">www&#46;sindromedeondine&#46;es</a>&#41;&#46; Patient recruitment started in March 2012&#46; Four families chose not to participate&#46; The patients and&#47;or legal guardians signed the informed consent form for participation&#46; The Spanish clinicians in charge of these patients&#44; one of whom is the Spanish registry coordinator&#44; were given access to the online registry&#46; Clinical data were entered by the participating clinicians and reviewed by the Spanish Registry coordinator&#46; The data are updated periodically&#44; and the last update took place in December 2015&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The following data were collected&#58; date and country of birth&#44; sex&#44; ethnicity&#44; pregnancy&#44; delivery and neonatal period&#46; Clinical manifestations at onset and during the course of disease &#40;respiratory&#44; gastrointestinal&#44; neurologic&#44; cardiovascular&#44; ophthalmologic&#44; endocrine&#44; oncological&#44; and other&#41; and comorbidities&#46; Diagnosis&#58; date&#44; tests performed&#44; genetic testing&#44; mutation found&#46; Treatment&#58; use of and changes in ventilatory support techniques&#59; surgery&#46; Length of hospital stay&#46; Social factors&#58; school attendance&#44; educational attainment&#44; initial employment&#46; Data related to death&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">We conducted a cross-sectional observational study&#46; We have expressed the data using the mean&#44; median&#44; standard deviation and range of quantitative variables and the absolute and relative frequency of qualitative variables&#46; When the data permitted&#44; we conducted hypothesis tests&#58; we compared the mean lengths of hospital stay in days by means of the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test and analysed the association between the frequency of comorbidities and the different mutations using linear regression&#46; The statistical analysis was performed with SPSS version 15&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">During the period under study &#40;March 2012 to December 2015&#41;&#44; data were entered and updated for 38 patients born between 1987 and 2013&#44; with a mean age of 13&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;45 years &#40;median&#44; 11&#46;35 months&#59; range&#44; 5 months&#8211;28&#46;6 years&#41;&#46; Thirteen patients &#40;34&#46;2&#37;&#41; were older than 18 years&#46; Seventeen &#40;44&#46;7&#37;&#41; were male&#44; and twenty one &#40;55&#46;3&#37;&#41; female&#46; The regional origin of the patients was as follows&#58; seven from Madrid&#44; six from Andalusia&#44; five from Castilla-La Mancha&#44; five from Catalonia&#44; three from Murcia&#44; three from the Basque Country&#44; two from arago&#44; two from valencia one from the Cnaray Islands&#44; one from Castilla Le&#243;n&#44; one from Extremadura&#44; one from the Balearic Islands&#44; and one from Navarra&#46; Twenty-two researchers from 19 Spanish hospitals participated in the study&#44; and are named in the list of authors&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Three patients died &#40;7&#46;8&#37;&#41;&#44; all of them unexpectedly and out of the hospital&#44; two during their sleep and one by accident&#46; Their ages at the time of death were 5 months&#44; 13 months and 15 years&#44; respectively&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Genotypes&#44; phenotypes and genotype-phenotype correlation</span><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">PHOX2B</span> screening was performed in 37 patients at the Spanish CCHS referral laboratory&#44; Institute of Medical and Molecular Genetics &#40;INGEMM&#41;&#44; Hospital Universitario La Paz&#44; Madrid&#46; Mutations were detected in thirty-two patients &#40;86&#46;4&#37;&#41;&#59; thirty &#40;93&#37;&#41; were PARMs and two &#40;6&#46;6&#37;&#41; were NPARMs &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Genotypes 20&#47;25&#44; 20&#47;26 and 20&#47;27 amounted to 84&#46;3&#37; of all detected mutations&#46; No <span class="elsevierStyleItalic">PHOX2B</span> mutations were found in four children&#46; Two received a diagnosis of ROHHAD syndrome based on their clinical presentation&#46; In the first case hypoventilation onset was at age 10<span class="elsevierStyleHsp" style=""></span>yrs&#44; whereas the second case presented neonatal hypoventilation during non-REM sleep&#46; For the remaining two patients&#44; the result of the genetic test is unknown&#44; for the first one and no genetic test was performed in the second case&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the referred comorbidities and their association with the different mutations&#59; there was a high prevalence of ocular involvement &#40;47&#46;3&#37;&#41;&#46; Two patients underwent urgent surgery for volvulus of the gastrointestinal tract&#46; Five patients &#40;13&#46;1&#37;&#41; had low glucose levels&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Due to the low number of registered patients presenting with NPARM mutations&#44; we were not able to establish clear genotype&#47;phenotype correlations differences between patients with PARM and patients with NPARM&#46; However&#44; structural disorders &#40;ANS tumours&#44; Hirschsprung disease&#41; tended to be associated with NPARMs&#44; while functional disorders &#40;heart rate abnormalities&#44; hypoglycaemia&#44; etc&#46;&#41; were associated with PARMs &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Within the group of patients with PARM&#44; ANS disorders were more frequent and severe in patients with longer expansions &#40;20&#47;27 &#91;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;014&#93; and 20&#47;33 &#91;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;003&#93;&#59; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Initial clinical presentation forms</span><p id="par0075" class="elsevierStylePara elsevierViewall">Thirty patients &#40;79&#37;&#41; had typical clinical symptoms at onset and required MV starting in the neonatal period &#40;29 from the first day of life&#44; one later&#41; without associated cardiorespiratory disease or any other clinical reason&#59; a <span class="elsevierStyleItalic">PHOX2B</span> mutation was detected in 28 &#40;93&#46;3&#37;&#41; of them&#44; no mutation was detected in one patient&#44; and the results for the other patient are unknown&#46; In eight patients &#40;21&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41; the clinical presentation at onset was different and&#47;or the need for MV occurred or was identified at later ages &#40;late onset&#47;delayed diagnosis&#41;&#46; Genetic testing detected a PHOX2B mutation in four out of eight of these cases &#40;50&#37;&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Type of ventilatory support</span><p id="par0080" class="elsevierStylePara elsevierViewall">Ventilatory support in the paediatric or neonatal intensive care unit&#58; at onset&#44; 35 patients &#40;92&#46;1&#37;&#41; received invasive MV following intubation&#44; and 18 &#40;47&#37;&#41; noninvasive ventilation &#40;NIV&#41;&#44; which was first used in year 2000&#46; Fifteen children &#40;39&#46;5&#37;&#41; received both types&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Ventilatory support at home&#58; &#40;a&#41; <span class="elsevierStyleItalic">via tracheostomy</span> &#40;TRACH&#41;&#58; 32 patients &#40;84&#46;2&#37;&#41; received ventilation via TRACH&#59; six &#40;15&#46;8&#37;&#41; never underwent tracheostomy&#59; the mean age of surgery was 7&#46;8 months<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;1 &#40;median&#44; 2&#46;6 months&#59; range&#44; 24 days&#8211;5&#46;75 years&#41;&#46; Eleven patients were decannulated &#40;34&#46;3&#37;&#41;&#59; the mean age of decannulation and switching to NIV was 13&#46;7 years<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;89 &#40;median&#44; 12&#46;66 years&#59; range&#44; 6&#46;12&#8211;20&#46;5 years&#41;&#46; Only one patient was aged less than 10 years at the time of decannulation&#46; &#40;b&#41; <span class="elsevierStyleItalic">Via mask</span>&#58; 19 patients &#40;50&#37;&#41; received ventilation via mask at home&#59; it was first used in 1998&#44; a milestone that was published by the clinicians&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the characteristics of the eight children ventilated via mask at the time of their first home discharge following diagnosis of CCHS&#58; five were infants with neonatal onset&#44; two of who had to switch to TRACH after experiencing cardiorespiratory arrest at home due to inefficient ventilation &#40;genotype&#58; 20&#47;33&#44; NPARM&#41;&#46; &#40;c&#41; <span class="elsevierStyleItalic">Phrenic nerve pacing</span> &#40;PNP&#41;&#58; A PNP device was implanted in four children aged&#44; 1&#46;2&#44; 8&#46;8&#44; 23&#44; and 24<span class="elsevierStyleHsp" style=""></span>yrs&#44; respectively&#46; The implantation of the PNP device failed in the youngest patients&#46; The three remaining patients with PNP ventilation had reached adult age in December 2015&#44; and were still needing MV around the clock &#40;PNP during the day time and via TRACH &#40;one patient&#41; or via mask &#40;two patients&#41; at night time&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">As of December 2015&#44; twenty-two patients have used only one type of ventilatory support&#44; thirteen patients two types&#44; and three patients three types&#46; None of the patients received negative-pressure ventilation&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the ventilatory support strategies used after the initial home discharge and in December 2015&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Lengths of hospital stay&#58; <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 4</a> present the length of the hospital stay preceding the use of MV at home&#46; The length of stay was significantly longer in patients with 20&#47;27 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;016&#41;&#44; discharged with a TRACH &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;004&#41; or admitted before year 2000 &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;000&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Social factors</span><p id="par0100" class="elsevierStylePara elsevierViewall">&#40;a&#41; <span class="elsevierStyleItalic">School attendance</span>&#58; of the 34 school-aged patients&#44; three &#40;8&#46;8&#37;&#41; attended special education programmes and 31 &#40;91&#37;&#41; attended regular school&#44; although ten of the latter &#40;29&#46;4&#37;&#41; required continuous special needs support&#46; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> shows the educational attainment of patients according to their ages&#46; Four patients older than 18 years &#40;30&#37;&#41; reached a higher education &#40;university&#44; 3&#59; post-secondary vocational school&#44; 1&#41;&#44; &#40;b&#41; <span class="elsevierStyleItalic">employment</span>&#58; four patients older than 18 years &#40;30&#37;&#41; had begun remunerated employment&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0105" class="elsevierStylePara elsevierViewall">This is the first comprehensive report on Spanish patients with CCHS&#46; Due to its low prevalence and the absence of national reference centers in Spain for the management of CCHS patients&#44; as recommended and practiced in other countries<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">2</span></a> &#40;France<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">24</span></a>&#44; United States<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a>&#41;&#44; the implementation of the CCHS European Registry in Spain has required the efforts and collaboration of 19 Hospitals and 22 health care professionals&#44; allowing the recruitment of 38 CCHS patients&#46; The launching of the Spanish reference laboratory for the genetic diagnosis of CCHS is the first significant step taken towards this goal&#44; which is an area for improvement&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">One third of the registered Spanish CCHS patients are older than 18<span class="elsevierStyleHsp" style=""></span>yrs as of December 2015&#46; Their long survival being the consequence of the successfull at-home MV support and the continuous care and support provided by their families&#46; Their entry into adulthood poses the challenge of the difficult transition of these chronically ill patients from paediatric care &#40;i&#46;e&#46; with a close follow-up&#41; to adult clinical care&#44; i&#46;e&#46; to clinicians less experienced with this rare disease and therefore offering less protection to the patients&#46; For this reason in some countries CCHS adult patients are followed by specialized reference centers in collaboration with clinical specialist&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a> Living independently&#44; becoming self-sufficient&#44; living as a couple and entering working life may pose challenges to these young adults who sleep with a ventilator&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The neurocognitive development of patients with CCHS is influenced by disease-related factors&#44; comorbidities and the permanent risk of hypoxaemia and hypercapnia&#44; especially during sleep&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">28&#8211;30</span></a> Nevertheless&#44; most Spanish patients have attended regular schools and four have attended higher education institutions&#44; although one third required continued special needs support&#46; For this reason&#44; optimising the care of Spanish children with CCHS requires regular psychoeducational assessments and curriculum planning in order to promptly detect and manage any learning difficulties&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The type&#44; frequency&#44; and genotype-phenotype correlations identified in this study were consistent with those reported in previous case series&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">14</span></a> Although&#44; as we mentioned above&#44; the low number of patients with NPARMs in our study precluded comparative analyses&#59; in contrast&#44; in our cohort&#44; ANS tumours were absent in patients with PARMs and Hirschsprung disease was more prevalent in patients with 20&#47;33 and NPARM genotypes&#46; Thus&#44; genetic testing is essential for the diagnosis of the disease and in guiding the multidisciplinary management and regular followup according to genotype-based protocols&#44; as recommended by the American Thoracic Society &#40;ATS&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">2&#44;15</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">As for the comorbidities&#44; five patients &#40;13&#37;&#41; had hypoglycaemia&#44; as compared to 8&#37; in the series published by Vanderlaan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">8</span></a>&#59; this complication has been rarely reported&#44; and even gone unmentioned in publications by experts<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">2</span></a>&#59; yet it is of great clinical relevance&#44; as hypoglycaemia has a considerable impact in the daily life of affected children and their families&#44; both due to its symptoms and to the measures required to control it&#44; which are not easy to achieve&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a> Two patients &#40;genotypes 20&#47;27&#44; 20&#47;33&#41; required urgent laparotomy due to gastrointestinal volvulus&#44; a complication which has not been previously reported by other authors&#44; although it may have been included in the broader category of intestinal motility disorders&#46; Ophthalmological problems are very frequent overall&#44; and were found in nearly half of the Spanish patients&#44; as happened in the series published by Vanderlaan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">8</span></a> Patwari et al<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">5</span></a> described an impaired pupillary response to light&#46; Therefore&#44; regular ophthalmologic evaluations including pupillometry are needed to prevent potential negative repercussions of visual abnormalities on learning and development&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Symptoms of central hypoventilation may go unnoticed or be misinterpreted leading to delayed diagnosis&#44; especially in patients with milder mutations&#44; as happened in three of our patients with the 20&#47;25 genotype&#44; although it also happened in the case of infant with a 20&#47;33 genotype who received an initial diagnosis of Hirschsprung disease&#46; Delays in diagnosis result in chronic hypoxia and hypercapnia&#44; which impair neurodevelopment<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a>&#59; their prevention is an area for improvement that calls for maintaining a high level of surveillance in patients with unexplained clinical findings such as episodes of cyanosis&#44; lethargy&#44; pulmonary hypertension&#44; need for MV due to mild infections or after anaesthesia&#44; seizures or neurodevelopmental delay&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The choice of ventilatory support modality in each patient and at each life stage is very important for the optimisation of care&#46; Ventilation via TRACH is the most frequently used technique in Spanish children with CCHS in the first decade of life&#44; consistent with previous reports in the literature&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">8</span></a> Different authors and the ATS recommend ventilation by TRACH during the early years of life due to its safety and in order to guarantee optimal neurodevelopmental outcomes&#44; avoiding switching to NIV before age 6&#8211;8 years&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">15</span></a> However&#44; this is subject to controversy&#44; as there are no studies analysing the impact of the choice of ventilatory support modality on neurodevelopment&#46; Costa Orvay et al&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">32</span></a> described the failure of NIV in two infants with CCHS in contrast to the experience of other authors<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">33</span></a>&#59; in the series published by Vanderlaan et al&#46;&#44; 14&#46;3&#37; of 196 patients never received ventilation via TRACH&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">8</span></a> a percentage similar to that found in our study &#40;15&#46;8&#37;&#41;&#46; We found that eight patients had been managed from the beginning and home discharged with mask ventilation and without TRACH&#44; five of whom had onset during the neonatal period&#58; the two with the most severe phenotypes &#40;20&#47;33&#44; NPARM&#41; had to switch to ventilation by TRACH after experiencing cardiorespiratory arrest at home&#44; while the other three&#44; who had milder mutations &#40;20&#47;25&#44; 20&#47;25&#44; no mutation&#41;&#44; continued with mask ventilation&#46; A factor to consider in addition to genotype severity when NIV is used in younger children is the negative impact that the interface may have on facial development in the long term&#44;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">34&#44;35</span></a> which we did not analyse in this study&#46; Given all of the above&#44; it is advisable to use TRACH as the initial modality in children with early-onset CCHS&#44; considering NIV as the alternative initial modality for very specific patients&#44; such as babies with milder phenotypes associated with milder hypoventilation and no comorbidities&#44; or patients with late onset&#46; The use of NIV should always be combined with close monitoring and preventive measures aimed to avoid facial deformities &#40;alternating interfaces&#44; use of full-face mask or negative pressure ventilation&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">36&#44;37</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Phrenic nerve pacing associated with other modalities was only used by three Spanish patients&#44; all of whom were dependent on 24-h a day MV&#44; consistent with the reports of other authors&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a> However&#44; PNP was used only in adolescents or adults only ventilated during sleep<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">8&#44;27</span></a> who have been decannulated and no longer use a mask&#46; The drawbacks of PNP are the surgery needed for implanting the device and the technical or infectious complications&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a> A new device that directly stimulates the diaphragm could improve this approach&#44; although there is still little evidence on its use&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">40</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">In our patients&#44; the transition from TRACH to NIV took place at a mean age of 13&#46;7 years&#44; which is double the minimum age recommended for safety &#40;6&#8211;8 years&#41;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">15</span></a>&#59; only one child transitioned before age 10 years&#44; and various factors that were not analysed in the study influenced the case-by-case decision of the timing for the switch&#58; advantages&#47;disadvantages&#44; attitudes and wishes of patients and parents&#44; or the medical team experience&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">The main limitation of this study is that the Registry has not recruited every Spanish patient with CCHS because some families declined to participate and there are probably additional patients who have not been diagnosed or remain unknown&#46; Using the data of known patients and the demographic data published by the Instituto Nacional de Estad&#237;stica of Spain &#40;National Institute of Statistics&#44; <a href="http://www.ine.es/inebmenu/mnu_dinamicapob.htm">http&#58;&#47;&#47;www&#46;ine&#46;es&#47;inebmenu&#47;mnu&#95;dinamicapob&#46;htm</a>&#41;&#44; we estimate a CCHS prevalence of 3&#46;5 per 1000000 live births&#59; however&#44; if we take the prevalence in France as a reference&#44;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">24</span></a> approximately two children would be born with CCHS in Spain every year&#44; and there would be 17 individuals with CCHS that have yet to be identified&#46; We would need to increase our collaborative efforts in order to identify them&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">In short&#44; the introduction of the European Registry of CCHS patients in Spain has allowed us to identify relevant factors for the purpose of improving their clinical management&#58; the absence of reference hospitals in Spain&#44; the importance of genetic testing and education strategies&#44; and some limitations of different ventilatory support modalities&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Funding</span><p id="par0160" class="elsevierStylePara elsevierViewall">This study was partially funded by grant FIS08&#47;90233 &#40;Angel Campos-Barros&#41;&#46; The design&#44; development and maintenance of the European registry have been funded by the <span class="elsevierStyleGrantSponsor" id="gs1">Consumer&#44; Health and Food Executive Agency of the European Commission</span>&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflicts of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Congenital central hypoventilation syndrome &#40;CCHS&#41; is a very rare genetic disease&#46; In 2012 the European Central Hypoventilation Syndrome &#40;EuCHS&#41; Consortium created an online patient registry in order to improve care&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Aim</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To determine the characteristics and outcomes of Spanish patients with CCHS&#44; and detect clinical areas for improvement&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Materials and method</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">An assessment was made on the data from Spanish patients in the European Registry&#44; updated on December 2015&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The Registry contained 38 patients&#44; born between 1987 and 2013&#44; in 18 hospitals&#46; Thirteen &#40;34&#46;2&#37;&#41; were older than 18 years&#46; Three patients had died&#46; Genetic analysis identified <span class="elsevierStyleItalic">PHOX2B</span> mutations in 32 &#40;86&#46;5&#37;&#41; out of 37 patients assessed&#46; The 20&#47;25&#44; 20&#47;26 and 20&#47;27 polyalanine repeat mutations &#40;PARMs&#41; represented 84&#46;3&#37; of all mutations&#46; Longer PARMs had more&#44; as well as more severe&#44; autonomic dysfunctions&#46; Eye diseases were present in 47&#37;&#44; with 16&#37; having Hirschsprung disease&#44; 13&#37; with hypoglycaemia&#44; and 5&#37; with tumours&#46; Thirty patients &#40;79&#37;&#41; required ventilation from the neonatal period onwards&#44; and 8 &#40;21&#37;&#41; later on in life &#40;late onset&#47;presentation&#41;&#46; Eight children &#40;21&#37;&#41; were using mask ventilation at the first home discharge&#46; Five of them were infants with neonatal onset&#44; two of them&#44; both having a severe mutation&#44; were switched to tracheostomy after cardiorespiratory arrest at home&#46; Approximately one-third &#40;34&#46;3&#37;&#41; of patients were de-cannulated and switched to mask ventilation at a mean age of 13&#46;7 years&#46; Educational reinforcement was required in 29&#46;4&#37; of children attending school&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The implementation of the EuCHS Registry in Spain has identified some relevant issues for optimising healthcare&#44; such as the importance of genetic study for diagnosis and assessment of severity&#44; the high frequency of eye disease and educational reinforcement&#44; as well as some limitations in ventilatory techniques&#46;</p></span>"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El s&#237;ndrome de hipoventilaci&#243;n central cong&#233;nita &#40;SHCC&#41; es una enfermedad gen&#233;tica muy rara causada por mutaciones en <span class="elsevierStyleItalic">PHOX2B</span>&#59; en 2010 se cre&#243; el Consorcio Europeo del S&#237;ndrome de Hipoventilaci&#243;n Central&#44; que en 2012 implant&#243; un Registro online de pacientes para optimizar su cuidado&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Conocer las caracter&#237;sticas y la evoluci&#243;n de los pacientes espa&#241;oles con SHCC y detectar &#225;reas de mejora&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Materiales y m&#233;todo</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se analizaron los datos actualizados en diciembre del 2015 de los pacientes espa&#241;oles del Registro europeo&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se registr&#243; a 38 pacientes&#44; nacidos entre 1987 y 2013&#44; procedentes de 18 hospitales&#46; El 34&#44;2&#37; eran mayores de 18 a&#241;os&#46; Han fallecido 3 pacientes&#46; Aportaban estudio del gen <span class="elsevierStyleItalic">PHOX2B</span> 37 &#40;97&#44;3&#37;&#41;&#44; 32 &#40;86&#44;5&#37;&#41; con mutaci&#243;n&#46; Los genotipos 20&#47;25&#44; 20&#47;26 y 20&#47;27 representaron el 84&#44;3&#37; de las mutaciones&#46; Las disautonom&#237;as fueron m&#225;s frecuentes y graves en portadores de genotipos con mayores expansiones de polialaninas&#46; El 47&#37; de pacientes asociaba alteraciones oculares&#44; el 16&#37; Hirschsprung&#44; el 13&#37; hipoglucemias y el 5&#37; tumores&#46; Treinta pacientes &#40;79&#37;&#41; debutaron en el periodo neonatal y 8 &#40;21&#37;&#41; posteriormente &#40;inicio&#47;diagn&#243;stico tard&#237;o&#41;&#46; Ocho ni&#241;os &#40;21&#37;&#41; recibieron inicialmente ventilaci&#243;n domiciliaria con mascarilla&#59; 5 eran lactantes con comienzo neonatal&#44; 2 de ellos precisaron cambio a traqueostom&#237;a tras presentar parada cardiorrespiratoria&#59; ambos ten&#237;an mutaciones graves&#46; Han sido decanulados y transferidos a mascarilla el 34&#44;3&#37; de los pacientes &#40;edad media&#58; 13&#44;7 a&#241;os&#41;&#46; El 29&#44;4&#37; de los ni&#241;os escolarizados precisaron refuerzo educativo&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusi&#243;n</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La implementaci&#243;n del Registro en Espa&#241;a de pacientes con SHCC ha permitido identificar aspectos relevantes para optimizar sus cuidados&#44; tales como la importancia del estudio gen&#233;tico para el diagn&#243;stico y la estimaci&#243;n de gravedad&#44; la frecuencia elevada de alteraciones oculares y de necesidad de refuerzo educativo&#44; y algunas limitaciones de las t&#233;cnicas ventilatorias&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0040">Please cite this article as&#58; Garc&#237;a Teresa MA&#44; Porto Abal R&#44; Rodr&#237;guez Torres S&#44; Garc&#237;a Urabayen D&#44; Garc&#237;a Mart&#237;nez S&#44; Trang H&#44; et al&#46; Pacientes espa&#241;oles con s&#237;ndrome de hipoventilaci&#243;n central incluidos en el Registro europeo&#46; Datos del 2015&#46; An Pediatr &#40;Barc&#41;&#46; 2017&#59;86&#58;255&#8211;263&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0045">Members of the SHCC Working Group are listed in <a class="elsevierStyleCrossRef" href="#sec0055">Appendix A</a>&#46;</p>"
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            "apendice" => "<p id="par0175" class="elsevierStylePara elsevierViewall">Ana Llorente de la Fuente&#58; Cuidados Intensivos Pedi&#225;tricos&#44; Hospital Doce de Octubre&#44; Madrid&#44; Spain</p> <p id="par0180" class="elsevierStylePara elsevierViewall">Arturo Hern&#225;ndez Gonz&#225;lez&#58; Cuidados Intensivos Pedi&#225;tricos&#44; Hospital Puerta del Mar&#44; C&#225;diz&#44; Spain</p> <p id="par0185" class="elsevierStylePara elsevierViewall">Amaya Bustinza Arriortua&#58; Cuidados Intensivos Pedi&#225;tricos&#44; Hospital Gregorio Mara&#241;&#243;n&#44; Madrid&#44; Spain</p> <p id="par0190" class="elsevierStylePara elsevierViewall">Jes&#250;s de la Cruz Moreno&#58; Pediatr&#237;a&#44; Hospital Universitario Materno Infantil&#44; Ja&#233;n&#44; Spain</p> <p id="par0195" class="elsevierStylePara elsevierViewall">Mart&#237; Pons Odena&#58; Cuidados Intensivos Pedi&#225;tricos&#44; Hospital Sant Joan de D&#233;u&#44; Barcelona&#44; Spain</p> <p id="par0200" class="elsevierStylePara elsevierViewall">Purificaci&#243;n Ventura Faci&#58; Neonatolog&#237;a&#44; Hospital Lozano Blesa&#44; Zaragoza&#44; Spain</p> <p id="par0205" class="elsevierStylePara elsevierViewall">Laura Rubio Ortega&#58; Hospitalizaci&#243;n a Domicilio Pedi&#225;trica&#44; Hospital General Universitario&#44; Alicante&#44; Spain</p> <p id="par0210" class="elsevierStylePara elsevierViewall">Estela P&#233;rez Ruiz&#58; Neumolog&#237;a Infantil&#44; Hospital Carlos Haya&#44; M&#225;laga&#44; Spain</p> <p id="par0215" class="elsevierStylePara elsevierViewall">Antonio Aguilar Fern&#225;ndez&#58; Neumolog&#237;a Pedi&#225;trica&#44; Hospital Materno Infantil&#44; Las Palmas&#44; Spain</p> <p id="par0220" class="elsevierStylePara elsevierViewall">Amaya P&#233;rez Oc&#243;n&#58; Cuidados Intensivos Pedi&#225;tricos&#44; Complejo Hospitalario de Navarra&#44; Pamplona&#44; Navarra&#44; Spain</p> <p id="par0225" class="elsevierStylePara elsevierViewall">Borja Osona&#58; Neumolog&#237;a Pedi&#225;trica&#44; Hospital Son Espases&#44; Palma de Mallorca&#44; Islas Baleares&#44; Spain</p> <p id="par0230" class="elsevierStylePara elsevierViewall">Isabel Delgado Pecellin&#58; Neumolog&#237;a Pedi&#225;trica&#44; Hospital Virgen del Roc&#237;o&#44; Sevilla&#44; Spain</p> <p id="par0235" class="elsevierStylePara elsevierViewall">Ignacio Arroyo Carrera&#58; Neonatolog&#237;a&#44; Hospital San Pedro de Alc&#225;ntara&#44; C&#225;ceres&#44; Spain</p> <p id="par0240" class="elsevierStylePara elsevierViewall">Javier Sayas Catal&#225;n&#58; Neumolog&#237;a&#44; Hospital Doce de Octubre&#44; Madrid&#44; Spain</p> <p id="par0245" class="elsevierStylePara elsevierViewall">Elvira Gonz&#225;lez Salas&#58; Cuidados Intensivos Pedi&#225;tricos&#44; Hospital Universitario de Salamanca&#44; Salamanca&#44; Spain</p> <p id="par0250" class="elsevierStylePara elsevierViewall">Carlos Martin de Vicente&#58; Neumolog&#237;a Pedi&#225;trica&#44; Hospital Miguel Servet&#44; Zaragoza&#44; Spain</p>"
            "etiqueta" => "Appendix A"
            "titulo" => "List of members of the Spanish Working Group of the SHCC"
            "identificador" => "sec0055"
          ]
        ]
      ]
    ]
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        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Ventilatory support modalities used &#40;bars&#41; and number of patients supported by each modality at home discharge and as of December 2015&#46;</p> <p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">NIV&#44; noninvasive ventilation with mask&#59; PNP&#44; phrenic nerve pacing&#59; TRACH&#44; tracheostomy&#46;</p>"
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      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Number of patients that reach each level of educational attainment&#46; We divided patients in two age groups&#58; &#60;18 years &#40;25 patients&#41; and &#8805;18 years &#40;13 patients&#41;&#46; Ten children required academic support&#46;</p>"
        ]
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      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
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            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">ANS&#44; autonomic nervous system&#59; NPARM&#44; nonpolyalanine repeat expansion mutation&#59; PARM&#44; polyalanine repeat expansion mutation&#59; PT&#44; patient&#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="" valign="top" scope="col">&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">20&#47;25&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">20&#47;26&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">20&#47;27&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">20&#47;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Total PARMs</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">NPARMs</th><th class="td" title="table-head  " align="left" valign="top" scope="col">No mutation&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">Not tested&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Total</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&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">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#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">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#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">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#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">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#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">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#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">&#40;&#37;&#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">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#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">&#40;&#37;&#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">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>5&#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">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#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">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>38&#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">&#40;&#37;&#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">ANS tumours&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;5&#46;2&#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">Hirschsprung disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;16&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#95;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;15&#46;8&#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">Gastrointestinal volvulus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;6&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;5&#46;2&#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">Syncope&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;13&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;10&#46;5&#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">Dizziness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;7&#46;9&#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">Pacemaker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;6&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;5&#46;2&#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">Seizures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;36&#46;8&#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">Breath holding spells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;13&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;13&#46;1&#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">Hypoglycaemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;16&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;13&#46;1&#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">Ocular disturbances&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;56&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;47&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Mean number comorbidities&#47;PT&#44; <span class="elsevierStyleItalic">P</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Mean length of stay in days&#44;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a><span class="elsevierStyleItalic">P</span></td><td class="td" title="table-entry  " align="char" valign="top">228&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">215&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">429&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="center" valign="top">282</td><td class="td" title="table-entry  " colspan="2" align="center" valign="top">425</td><td class="td" title="table-entry  " align="char" valign="top">165&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">152&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="center" valign="top">271</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">&#60;&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;&#46;016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " colspan="2" align="center" valign="top">&#60;&#46;94</td><td class="td" title="table-entry  " align="char" valign="top">&#60;&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;&#46;92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Genotype&#8211;phenotype correlations&#46; Absolute frequency and percentage &#40;in parentheses&#41; of patients with different autonomic nervous system comorbidities in each group and subgroup of <span class="elsevierStyleItalic">PHOX2B</span> mutations &#40;PARM &#91;20&#47;25&#44; 20&#47;26&#44; 20&#47;27&#44; 20&#47;33&#93;&#44; NPARM&#41;&#46;</p>"
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">CRA&#44; cardiorespiratory arrest&#59; DOL&#44; days of life&#59; MRI&#44; magnetic resonance imaging&#59; MV&#44; mechanical ventilation&#59; NIV&#44; noninvasive mechanical ventilation with mask&#59; NB&#44; newborn&#59; ROHHAD&#58; rapid-onset obesity with hypoventilation&#44; hypothalamic dysfunction and autonomic dysregulation&#59; TPN&#44; total parenteral nutrition&#59; TRACH&#44; tracheostomy&#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">Previous symptoms&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">Age at initiation of MV&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">Symptoms at onset &#40;ventilation modality&#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">Mutation&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">1&#46; Healthy NB&#44; discharge home<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Cyanosis&#44; hypercapnia without distress&#44; need for MV &#40;TRACH&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#47;26&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">2&#46; Healthy NB&#44; discharge home&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lethargy&#44; feeding refusal&#44; cyanosis&#44; hypercapnia without respiratory distress&#44; need for MV &#40;TRACH&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#47;25&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">3&#46; NB 1st DOL&#58; cyanotic episodes&#44; clinical sepsis diagnosis&#44; antibiotherapy&#44; home discharge&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">46 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Readmitted for cyanosis&#44; hypercapnia without distress&#44; need for MV &#40;TRACH&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#47;25&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">4&#46; NB 1st DOL&#58; cyanotic episodes&#44; hypoglycaemia&#44; clinical sepsis&#44; antibiotherapy&#44; home discharge&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Readmitted for lethargy&#44; feeding refusal&#44; cyanosis&#44; hypercapnia without respiratory distress&#44; oedema&#44; liver disease&#44; need for MV &#40;TRACH&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#47;25&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">5&#46; NB&#44; 3rd DOL&#44; gastrointestinal symptoms&#44; requires TPN&#59; 1 month&#58; hypercapnia without evaluation&#59; 3 months&#58; diagnosis of Hirschsprung disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;8 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bronchiolitis&#44; need for MV &#40;NIV&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#47;33&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">6<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">b</span></a>&#46; Sleep disorders&#44; 14 months&#58; primary pulmonary hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;6 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Pneumonia&#44; hypoxaemia&#44; convulsive seizures&#44; need for MV &#40;TRACH&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not tested&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">7<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">b</span></a>&#46; Healthy until 7 months prior&#44; when patient had onset of polyphagia&#44; rapid weight gain&#44; enuresis&#44; sleep disturbances and profuse sweating&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;9 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Apnoea&#44; cyanosis&#44; CRA&#46; ROHHAD&#58; obesity&#44; central hypoventilation&#44; hypothalamic dysfunction&#44; thoracic ganglioneuroblastoma&#44; need for MV &#40;TRACH&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No mutation&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">8&#46; Healthy to 3 years&#44; when patient had onset of polyphagia&#44; gained 14<span class="elsevierStyleHsp" style=""></span>kg in a few months&#44; polyuria&#44; profuse sweating&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;2 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Episodes of central obstructive apnoea&#46; Bradycardia&#44; Raynaud disease&#44; ROHHAD&#58; obesity&#44; central hypoventilation&#44; hypothalamic dysfunction &#40;elevated TSH&#41;&#44; need for MV &#40;NIV&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No mutation&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">9&#46; Healthy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#46;4 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Coma&#44; hypercapnia&#44; suspected encephalitis resolved with MV&#44; normal MRI&#44; persistent central hypoventilation&#44; need for MV &#40;NIV&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No mutation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1403216.png"
              ]
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          "notaPie" => array:2 [
            0 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Includes a patient with neonatal onset that took place after home discharge&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020"><span class="elsevierStyleItalic">Source</span>&#58; S&#225;nchez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">17</span></a>&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Patients with late onset or delayed diagnosis of central hypoventilation syndrome&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
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        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">CPA&#44; cardiopulmonary arrest&#59; DOL&#44; days of life&#59; MV&#44; mechanical ventilation&#59; NPARM&#58; nonpolyalanine repeat expansion mutation&#59; PNP&#44; phrenic nerve pacing&#59; ROHHAD&#58; rapid-onset obesity with hypoventilation&#44; hypothalamic dysfunction and autonomic dysregulation&#59; TRACH&#44; tracheostomy&#46;</p>"
          "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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&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">Age at initiation of ventilation&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">Age at home discharge&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">Comorbidities&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">Mutation&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">Switch to different modality&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">Age at switch&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">Reason for switch&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">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1st DOL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;7 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#47;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1st DOL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;17 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#47;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1st DOL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;7 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No mutation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1st DOL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;43 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hirschsprung breath holding spells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#47;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; to TRACH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;7 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CPA at home&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">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1st DOL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;23 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NPARM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; to TRACH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;6 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">CPA at home&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">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;7 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;3 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hirschsprung&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#47;33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;2 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46; 3 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">ROHHAD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No mutation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&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">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#46;4 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#46;9 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Peripheral neuropathy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No mutation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#44; addition of PNP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22&#46;9 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Need for 24-h MV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1403219.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Patients who received noninvasive ventilation via mask as the first option and who remained under NIV after home discharge&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at4"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">NIV&#44; noninvasive ventilation with mask&#59; TRACH&#44; tracheostomy&#46;</p>"
          "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="table-head  " align="" valign="top" scope="col">&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">All patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Type of ventilatory support</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Type of onset</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Year of initial admission</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&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">&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>38&#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">TRACH<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#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">NIV<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#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">Neonatal<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#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">Late onset<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>8&#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">&#60;2000<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#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">&#8805;2000<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#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">Mean&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">271&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">319<a class="elsevierStyleCrossRef" href="#tblfn0035"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">304<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">566<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">118&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">Standard deviation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">313&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">336&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">344&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">392&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">53&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">Median&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">153&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">181&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">153&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">162&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">332&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">103&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">Range&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49&#8211;1165&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62&#8211;1165&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49&#8211;175&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51&#8211;1165&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49&#8211;259&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">154&#8211;1165&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49&#8211;212&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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