Case report
Long QT syndrome with mutations in three genes: A rare case
Síndrome do QT longo: mutação trigénica, um caso raro
Marina Fernandes
, Sílvia Martins Ribeiro, Victor Sanfins, António Lourenço
Corresponding author
Serviço de Cardiologia, Centro Hospitalar do Alto Ave, Guimarães, Portugal
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H&E staining (A) shows discrete fiber size variation, fiber splitting and internalized nuclei; Oil-red-O staining (B) shows increased lipid accumulation; PAS-staining (C) shows storage of excess glycogen; Excess glycogen deposits are also detectable at an ultrastructural level within and between the fibers (A-C) ×20 magnification (D) × 3000 magnification.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Josef Finsterer, Claudia Stöllberger, Martin Gencik, Romana Höftberger, Jasmin Rahimi, Johannes Mokocki" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Josef" "apellidos" => "Finsterer" ] 1 => array:2 [ "nombre" => "Claudia" "apellidos" => "Stöllberger" ] 2 => array:2 [ "nombre" => "Martin" "apellidos" => "Gencik" ] 3 => array:2 [ "nombre" => "Romana" "apellidos" => "Höftberger" ] 4 => array:2 [ "nombre" => "Jasmin" "apellidos" => "Rahimi" ] 5 => array:2 [ "nombre" => "Johannes" "apellidos" => "Mokocki" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0870255115001079" "doi" => "10.1016/j.repc.2014.11.018" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0870255115001079?idApp=UINPBA00004E" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204915001245?idApp=UINPBA00004E" "url" => "/21742049/0000003400000005/v1_201506091454/S2174204915001245/v1_201506091454/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S2174204915000768" "issn" => "21742049" "doi" => "10.1016/j.repce.2014.10.005" "estado" => "S300" "fechaPublicacion" => "2015-05-01" "aid" => "607" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Rev Port Cardiol. 2015;34:357.e1-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 7248 "formatos" => array:3 [ "EPUB" => 191 "HTML" => 6171 "PDF" => 886 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case report</span>" "titulo" => "High left ventricular outflow tract gradient: Aortic stenosis, obstructive hypertrophic cardiomyopathy or both?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "357.e1" "paginaFinal" => "357.e5" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Gradiente elevado no trato de saída do ventrículo esquerdo: estenose aórtica, miocardiopatia hipertrófica obstrutiva ou ambas?" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 917 "Ancho" => 3257 "Tamanyo" => 274226 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Transesophageal echocardiography: (left) malformed aortic valve with area calculated by planimetry of 0.6 cm<span class="elsevierStyleSup">2</span>; 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She had initially been diagnosed with epilepsy but tilt testing showed a vasodepressive response. Midodrine was prescribed, but without clinical improvement. No electrocardiographic records are available from that time.</p><p id="par0015" class="elsevierStylePara elsevierViewall">She was referred by her health center for cardiology consultation in our hospital due to continuing recurrent syncope; she reported episodes of presyncope and syncope, occasionally preceded by palpitations and sometimes triggered by standing.</p><p id="par0020" class="elsevierStylePara elsevierViewall">There was no other relevant medical history; her family history included the sudden death of her mother at age 46, with a history of type 2 diabetes and anatomopathological evidence of chronic ischemic heart disease.</p><p id="par0025" class="elsevierStylePara elsevierViewall">No abnormalities were detected on laboratory tests and transthoracic echocardiography revealed no significant alterations. The 12-lead electrocardiogram (ECG) performed at the cardiology consultation showed sinus rhythm and significant QTc prolongation (500–565 ms) (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>). She was taking carvedilol 12.5 mg twice daily but the dose could not be titrated due to symptomatic hypotension. In view of the result of the previous tilt test and the non-specific symptoms, it was decided to implant an event recorder. The patient reported several episodes of pre-syncope, which corresponded to periods of sinus tachycardia, and in one of these nonsustained polymorphic ventricular tachycardia (VT) was recorded (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>). It was accordingly decided to implant an implantable cardioverter-defibrillator (ICD). Around a month after the procedure remote monitoring recorded an appropriate shock for polymorphic VT (<a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>). Her beta-blocker therapy was changed to propanolol.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Molecular genetic testing identified the c.785delG mutation in heterozygosity in exon 4 of the <span class="elsevierStyleItalic">KCNH2</span> gene, which leads to the formation of a premature STOP codon in position 359 in the protein (p.Gly262AlafsX98). Two further mutations were found:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">–</span><p id="par0035" class="elsevierStylePara elsevierViewall">c.535G>A, in heterozygosity, in exon 3 of the <span class="elsevierStyleItalic">KCNQ1</span> gene, which leads to substitution of an amino acid at position 179 of the protein (p.Gly179Ser);</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">–</span><p id="par0040" class="elsevierStylePara elsevierViewall">c.3068G>A, in heterozygosity, in exon 17 of the <span class="elsevierStyleItalic">SCN5A</span> gene, which leads to substitution of an amino acid at position 1023 of the protein (p.Arg1023His).</p></li></ul></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0045" class="elsevierStylePara elsevierViewall">LQTS is a genetic disease characterized by significant prolongation of the QT interval, predisposing to ventricular arrhythmias and manifesting clinically with syncope, seizures or sudden death in individuals with structurally normal hearts.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1,2</span></a> The high incidence of vasovagal syncope and epilepsy in young individuals without structural heart disease means that diagnosis is often delayed or incorrect.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">4</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">According to the HRS/EHRA/APHRS expert consensus statement on inherited primary arrhythmia syndromes, LQTS is diagnosed: (a) in the presence of an LQTS risk score ≥3.5 in the absence of a secondary cause for QT prolongation and/or (b) in the presence of a pathogenic mutation in one of the LQTS genes or (c) in the presence of a QTc ≥500 ms in repeated 12-lead ECGs. LQTS can be diagnosed in the presence of a QTc between 480 and 499 ms in repeated ECGs in a patient with unexplained syncope in the absence of a secondary cause for QT prolongation or a pathogenic mutation.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The Schwartz score estimates the probability of a diagnosis of LQTS on the basis of clinical, electrocardiographic and family history criteria. It has two main limitations: although its sensitivity is high its specificity is low; and it does not include genetic testing as a diagnostic criterion, failing to identify 30% of asymptomatic carriers.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">5–8</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Mutations have been identified in several genes and new cases are frequently reported. The genes most often affected are <span class="elsevierStyleItalic">KCNQ1</span> (LQT1), <span class="elsevierStyleItalic">KCNH2</span> (LQT2) and <span class="elsevierStyleItalic">SCN5A</span> (LQT3).<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1–3,7,9</span></a> The first two lead to loss of function of potassium channels and the third causes gain of function in sodium channels. All three alter ion channels, destabilizing the membrane potential. Most mutations have an autosomal dominant inheritance pattern.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Clinical characteristics, particularly triggers of VT, and the electrocardiographic pattern of prolonged QT interval, can be used to correctly infer the genotype in 70–90% of cases.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">10</span></a> LQT1 is characterized by a broad T wave, and arrhythmias, being adrenergic-dependent, arise during exercise or emotional stress, while in LQT2 the T wave is narrow and notched and the most common triggers are emotional stress and auditory stimuli. In LQT3 the prolonged QT interval is mainly due to prolongation of the isoelectric ST segment, and events usually occur at rest or during sleep, demonstrating its low sensitivity to changes in the sympathetic nervous system and raising concerns regarding its response to beta-blocker therapy.<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">7,10</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">It is important to exclude drug use, hypothyroidism and electrolyte imbalance as causes of a prolonged QT interval; although a long QT can arise as a result of pharmacological therapy, this may also unmask previously occult LQTS.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Genetic testing, which identifies the mutation responsible in 50–70% of cases, is important to confirm the diagnosis, identify asymptomatic carriers, stratify risk for arrhythmic events and provide a basis for genetic counseling.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">7</span></a> It is essential to identify silent carriers, since they are at high risk for severe ventricular arrhythmias. Those at greatest risk are patients with LQT1 and LQT2 with QTc >500 ms and male patients with LQT3 irrespective of QT interval. Digenic and compound mutations are found in 8% of patients with LQTS and are associated with a more severe phenotype.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">12,13</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Our patient presented mutations in three different genes. The p.Gly262AlafsX98 mutation in the <span class="elsevierStyleItalic">KCNH2</span> gene has been described in patients with LQTS (Human Gene Mutation Database [HGMD] CD070027) and is known to be a cause of the condition.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">14</span></a> The mutations p.Gly179Ser in <span class="elsevierStyleItalic">KCNQ1</span> and p.Arg1023His in <span class="elsevierStyleItalic">SCN5A</span> have also been reported in LQTS (HGMD CM002321 and CM054857, respectively).<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">14</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">In all patients with a clinical or molecular diagnosis, drugs that prolong QT interval are contraindicated, and any electrolyte disturbances should be identified and treated. Beta-blockers are recommended in asymptomatic patients with QTc ≥470 ms and symptomatic patients with syncope or ventricular arrhythmias (class I recommendation), and can be useful in asymptomatic patients with QTc <470 ms (class IIa). Sympathetic denervation is recommended in high-risk patients in whom ICD implantation is contraindicated or refused and for those in whom beta-blockers are either not effective in preventing arrhythmias or not tolerated (class I).<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> ICD implantation is recommended in all patients who are survivors of a cardiac arrest and in those with VT or syncope under beta-blocker therapy.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">1,2</span></a> In patients with LQT3 and QTc >500 ms, sodium channel blockers can be useful in association with beta-blockers.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">1</span></a> There is evidence that nadolol and propanolol are the safest and most effective beta-blockers for these patients.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusions</span><p id="par0090" class="elsevierStylePara elsevierViewall">LQTS is a rare hereditary disease in patients without structural heart disease that is associated with a high risk of malignant VT and sudden death. ICD implantation is indicated after resuscitated sudden death or persistence of symptoms despite beta-blocker therapy. The case presented is of a patient with LQTS in whom mutations were identified in three different genes, which is a rare finding and is associated with worse prognosis.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Ethical disclosures</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Protection of human and animal subjects</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Confidentiality of data</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Right to privacy and informed consent.</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflicts of interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres521199" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec541759" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres521198" "titulo" => "Resumo" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec541760" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conclusions" ] 8 => array:3 [ "identificador" => "sec0025" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Right to privacy and informed consent." ] ] ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-08-14" "fechaAceptado" => "2014-10-10" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec541759" "palabras" => array:6 [ 0 => "Long QT syndrome" 1 => "Triple mutation" 2 => "KCNH2 gene" 3 => "KCNQ1 gene" 4 => "SCN5A gene" 5 => "Polymorphic ventricular tachycardia" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec541760" "palabras" => array:6 [ 0 => "Síndrome QT longo" 1 => "Mutação trigénica" 2 => "Gene KCNH2" 3 => "Gene KCNQ1" 4 => "Gene SCN5A" 5 => "Taquicardia ventricular polimórfica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Congenital long QT syndrome (LQTS) is a rare hereditary disease, with an incidence of 1 in 2000, characterized by prolonged ventricular repolarization and malignant ventricular tachyarrhythmias. We report the case of a 30-year-old woman, previously diagnosed with neurocardiogenic syncope, in whom LQTS was identified. The patient received an implantable cardioverter-defibrillator due to polymorphic ventricular tachycardia under beta-blocker therapy. Molecular genetic testing identified three mutations in heterozygosity in the <span class="elsevierStyleItalic">KCNH2</span>, <span class="elsevierStyleItalic">KCNQ1</span> and <span class="elsevierStyleItalic">SCN5A</span> genes, which is a rare finding and is associated with worse prognosis.</p></span>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A síndrome do QT longo congénito (SQTLC) é uma doença hereditária rara, com uma incidência de uma em cada 2000 pessoas, caracterizada por uma repolarização ventricular prolongada e por taquiarritmias ventriculares malignas.</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Reportamos o caso de uma doente de 30 anos, com diagnóstico prévio de síncope neurocardiogénica, em que identificamos a SQTLC. A doente implantou cardioversor-desfibrilhador implantável por taquicardia ventricular polimórfica apesar da terapêutica com bloqueador beta.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Foram identificadas nesta doente três mutações em heterozigotia nos genes KCNH2, KCNQ1 e SCN5A, achado raro que lhe confere um pior prognóstico.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Fernandes M, Martins Ribeiro S, Sanfins V, et al. Síndrome do QT longo: mutação trigénica, um caso raro. Rev Port Cardiol. 2015;34:359.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1413 "Ancho" => 2999 "Tamanyo" => 908493 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">12-lead electrocardiogram showing sinus rhythm and significant QTc prolongation (565 ms).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1324 "Ancho" => 2917 "Tamanyo" => 641816 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Polymorphic ventricular tachycardia detected on implantable event recorder.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1981 "Ancho" => 2999 "Tamanyo" => 491040 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Intracardiac electrogram from implantable cardioverter-defibrillator showing polymorphic ventricular tachycardia detected by remote monitoring.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:14 [ 0 => array:3 [ "identificador" => "bib0075" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "S.G. 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| 2018 June | 50 | 8 | 58 |
| 2018 May | 77 | 5 | 82 |
| 2018 April | 47 | 7 | 54 |
| 2018 March | 83 | 9 | 92 |
| 2018 February | 32 | 2 | 34 |
| 2018 January | 35 | 6 | 41 |
| 2017 December | 71 | 5 | 76 |
| 2017 November | 56 | 13 | 69 |
| 2017 October | 50 | 17 | 67 |
| 2017 September | 46 | 12 | 58 |
| 2017 August | 36 | 17 | 53 |
| 2017 July | 48 | 14 | 62 |
| 2017 June | 54 | 21 | 75 |
| 2017 May | 63 | 9 | 72 |
| 2017 April | 54 | 10 | 64 |
| 2017 March | 57 | 24 | 81 |
| 2017 February | 37 | 7 | 44 |
| 2017 January | 40 | 6 | 46 |
| 2016 December | 46 | 13 | 59 |
| 2016 November | 37 | 4 | 41 |
| 2016 October | 55 | 6 | 61 |
| 2016 September | 64 | 15 | 79 |
| 2016 August | 15 | 6 | 21 |
| 2016 July | 12 | 6 | 18 |
| 2016 June | 16 | 7 | 23 |
| 2016 May | 22 | 3 | 25 |
| 2016 April | 24 | 1 | 25 |
| 2016 March | 48 | 9 | 57 |
| 2016 February | 72 | 18 | 90 |
| 2016 January | 53 | 19 | 72 |
| 2015 December | 52 | 15 | 67 |
| 2015 November | 35 | 16 | 51 |
| 2015 October | 46 | 15 | 61 |
| 2015 September | 55 | 19 | 74 |
| 2015 August | 52 | 26 | 78 |
| 2015 July | 57 | 23 | 80 |
| 2015 June | 146 | 66 | 212 |
Show all
