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Life (Basel, Switzerland) Dec 2022PRKAG2 syndrome (PS) is a rare, early-onset autosomal dominant phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM), that mainly presents with ventricular... (Review)
Review
PRKAG2 syndrome (PS) is a rare, early-onset autosomal dominant phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM), that mainly presents with ventricular pre-excitation, cardiac hypertrophy and progressive conduction system degeneration. Its natural course, treatment and prognosis are significantly different from sarcomeric HCM. The clinical phenotypes of PRKAG2 syndrome often overlap with HCM due to sarcomere protein mutations, causing this condition to be frequently misdiagnosed. The syndrome is caused by mutations in the gene encoding for the γ2 regulatory subunit (PRKAG2) of 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK), an enzyme that modulates glucose uptake and glycolysis. PRKAG2 mutations (OMIM#602743) are responsible for structural changes of AMPK, leading to an impaired myocyte glucidic uptake, and finally causing storage cardiomyopathy. We describe the clinical and investigative findings in a family with several affected members (NM_016203.4:c.905G>A or p.(Arg302Gln), heterozygous), highlighting the various phenotypes even in the same family, and the utility of genetic testing in diagnosing PS. The particularity of this family case is represented by the fact that the index patient was diagnosed at age 16 with cardiac hypertrophy and ventricular pre-excitation while his mother, by age 42, only had Wolff−Parkinson−White syndrome, without left ventricle hypertrophy. Both the grandmother and the great-grandmother underwent pacemaker implantation at a young age because of conduction abnormalities. Making the distinction between PS and sarcomeric HCM is actionable, given the early-onset of the disease, the numerous life-threatening consequences and the high rate of conduction disorders. In patients who exhibit cardiac hypertrophy coexisting with ventricular pre-excitation, genetic screening for PRKAG2 mutations should be considered.
PubMed: 36556501
DOI: 10.3390/life12122136 -
Cureus Dec 2018Fainting is a common clinical presentation, with vagally mediated (neurocardiogenic) causes being the most common for syncope presentation to the emergency room, and for...
Fainting is a common clinical presentation, with vagally mediated (neurocardiogenic) causes being the most common for syncope presentation to the emergency room, and for hospital admissions. Classic teaching is that upright posture is a prerequisite for vagally mediated syncope (VMS) and that syncope in the supine position has more sinister causes. We present five patients, three males and two females, with a mean age of 44.4 (range 29-67) years, who presented with VMS in the supine position (sleep fainting). Four patients also had a history of classic upright syncope. Based on their clinical features and thorough investigations, we excluded other causes of loss of consciousness and diagnosed these patients to be having VMS in the supine position (sleep fainting). We further describe the management and follow-up of these patients. Sleep fainting/syncope is a new entity and has to be recognized for appropriate management. A diagnosis can be established if there is clinical suspicion, preserved left ventricular function without evidence of coronary artery disease, no high-risk electrocardiographic evidence of pre-excitation, long or short QT syndrome, Brugada syndrome or arrhythmogenic right ventricular dysplasia, and normal neurological work-up.
PubMed: 30820371
DOI: 10.7759/cureus.3751 -
Journal of the American Veterinary... Nov 2018
Topics: Accessory Atrioventricular Bundle; Animals; Cat Diseases; Cats; Electrocardiography; Pre-Excitation Syndromes
PubMed: 30398413
DOI: 10.2460/javma.253.10.1264 -
Medicine Aug 2022Abnormal development of the atrioventricular ring can lead to the formation of a bypass pathway and the occurrence of Wolff-Parkinson-White (WPW) syndrome. The genetic...
Abnormal development of the atrioventricular ring can lead to the formation of a bypass pathway and the occurrence of Wolff-Parkinson-White (WPW) syndrome. The genetic mechanism underlying the sporadic form of WPW syndrome remains unclear. Existing evidence suggests that both T-box transcription factor 3 (TBX3) and T-box transcription factor 2 (TBX2) genes participate in regulating annulus fibrosus formation and atrioventricular canal development. Thus, we aimed to examine whether single-nucleotide polymorphisms (SNPs) in the TBX3 and TBX2 genes confer susceptibility to WPW syndrome in a Han Chinese Population. We applied a SNaPshot SNP assay to analyze 5 selected tagSNPs of TBX3 and TBX2 in 230 patients with sporadic WPW syndrome and 231 sex- and age-matched controls. Haplotype analysis was performed using Haploview software. Allele C of TBX3 rs1061657 was associated with a higher risk of WPW syndrome (odds ratio [OR] = 1.41, 95% confidence interval [CI]: 1.08-1.83, P = .011) and left-sided accessory pathways (OR = 1.40, 95% CI: 1.07-1.84, P = .016). However, allele C of TBX3 rs8853 was likely to reduce these risks (OR = 0.71, 95% CI: 0.54-0.92, P = .011; OR = 0.70, 95% CI: 0.53-0.92, P = .011, respectively). The data revealed no association between TBX3 rs77412687, TBX3 rs2242442, or TBX2 rs75743672 and WPW syndrome. TBX3 rs1061657 and rs8853 are significantly associated with sporadic WPW syndrome among a Han Chinese population. To verify our results, larger sample sizes are required in future studies.
Topics: Accessory Atrioventricular Bundle; China; Humans; Polymorphism, Single Nucleotide; Wolff-Parkinson-White Syndrome
PubMed: 35960099
DOI: 10.1097/MD.0000000000030046 -
Kardiologia Polska Mar 2020
Topics: Accessory Atrioventricular Bundle; Arrhythmias, Cardiac; Humans; Prevalence; Risk Factors; Wolff-Parkinson-White Syndrome
PubMed: 32218386
DOI: 10.33963/KP.15248 -
Herzschrittmachertherapie &... Mar 2024In 1930, Wolff, Parkinson and White described the syndrome that bears their names. The mechanisms of supraventricular tachycardias were analyzed by brilliant... (Review)
Review
In 1930, Wolff, Parkinson and White described the syndrome that bears their names. The mechanisms of supraventricular tachycardias were analyzed by brilliant electrocardiography interpretation by Pick and Langendorf. Wellens and Durrer using electrophysiologic studies analyzed the tachycardia mechanism invasively. In Germany the group by Seipel and Breithardt as well as Neuss and Schlepper studied the tachycardia mechanisms and response to antiarrhythmic drugs invasively by electrophysiological studies. Following the first successful interruption of an accessory pathway by Sealy in 1967, surgeons and electrophysiologists cooperated in Germany. Two centers, Hannover and Düsseldorf were established. Direct current (DC) ablation of accessory pathways was introduced by Morady and Scheinman. Because of side effects induced by barotrauma of DC, alternative strategies were studied. In 1987, radiofrequency ablation was introduced and thereafter established as curative therapy of accessory pathways in all locations.
Topics: Humans; Wolff-Parkinson-White Syndrome; Pre-Excitation Syndromes; Tachycardia, Supraventricular; Tachycardia; Accessory Atrioventricular Bundle; Catheter Ablation; Electrocardiography
PubMed: 38427036
DOI: 10.1007/s00399-024-01000-6 -
Journal of Arrhythmia Dec 2021This is a case of antidromic AVRT in a patient with unapparent preexcitation, and we could successfully diagnose and treat with the careful interpretation of wide QRS...
This is a case of antidromic AVRT in a patient with unapparent preexcitation, and we could successfully diagnose and treat with the careful interpretation of wide QRS tachycardia. We should keep in mind that differentiation between intermittent and unapparent preexcitation is difficult, and some patients with unapparent preexcitation have short refractory periods of those accessory pathways, leading to sudden death.
PubMed: 34887962
DOI: 10.1002/joa3.12634 -
Human Molecular Genetics May 2018The PITX2 (paired-like homeodomain 2) gene encodes a bicoid-like homeodomain transcription factor linked with several human disorders. The main associated congenital...
The PITX2 (paired-like homeodomain 2) gene encodes a bicoid-like homeodomain transcription factor linked with several human disorders. The main associated congenital phenotype is Axenfeld-Rieger syndrome, type 1, an autosomal dominant condition characterized by variable defects in the anterior segment of the eye, an increased risk of glaucoma, craniofacial dysmorphism and dental and umbilical anomalies; in addition to this, one report implicated PITX2 in ring dermoid of the cornea and a few others described cardiac phenotypes. We report three novel PITX2 mutations-c.271C > T, p.(Arg91Trp); c.259T > C, p.(Phe87Leu); and c.356delA, p.(Gln119Argfs*36)-identified in independent families with typical Axenfeld-Rieger syndrome characteristics and some unusual features such as corneal guttata, Wolf-Parkinson-White syndrome, and hyperextensibility. To gain further insight into the diverse roles of PITX2/pitx2 in vertebrate development, we generated various genetic lesions in the pitx2 gene via TALEN-mediated genome editing. Affected homozygous zebrafish demonstrated congenital defects consistent with the range of PITX2-associated human phenotypes: abnormal development of the cornea, iris and iridocorneal angle; corneal dermoids; and craniofacial dysmorphism. In addition, via comparison of pitx2M64* and wild-type embryonic ocular transcriptomes we defined molecular changes associated with pitx2 deficiency, thereby implicating processes potentially underlying disease pathology. This analysis identified numerous affected factors including several members of the Wnt pathway and collagen types I and V gene families. These data further support the link between PITX2 and the WNT pathway and suggest a new role in regulation of collagen gene expression during development.
Topics: Animals; Anterior Eye Segment; Collagen Type I; Collagen Type V; Eye Abnormalities; Eye Diseases, Hereditary; Gene Editing; Gene Expression Regulation, Developmental; Glaucoma; Homeodomain Proteins; Humans; Mutation; Pedigree; Transcription Factors; Wnt Signaling Pathway; Wolff-Parkinson-White Syndrome; Zebrafish; Zebrafish Proteins; Homeobox Protein PITX2
PubMed: 29506241
DOI: 10.1093/hmg/ddy074 -
Anatolian Journal of Cardiology Feb 2017
Topics: Adult; Diagnosis, Differential; Dizziness; Electrocardiography; Electrocardiography, Ambulatory; Female; Humans; Pre-Excitation Syndromes
PubMed: 28209931
DOI: 10.14744/AnatolJCardiol.2016.7200 -
Journal of Internal Medicine Dec 2014The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that regulates cellular and whole-body energy balance. A recently reported crystal... (Review)
Review
The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that regulates cellular and whole-body energy balance. A recently reported crystal structure has illuminated the complex regulatory mechanisms by which AMP and ADP cause activation of AMPK, involving phosphorylation by the upstream kinase LKB1. Once activated by falling cellular energy status, AMPK activates catabolic pathways that generate ATP whilst inhibiting anabolic pathways and other cellular processes that consume ATP. A role of AMPK is implicated in many human diseases. Mutations in the γ2 subunit cause heart disease due to excessive glycogen storage in cardiac myocytes, leading to ventricular pre-excitation. AMPK-activating drugs reverse many of the metabolic defects associated with insulin resistance, and recent findings suggest that the insulin-sensitizing effects of the widely used antidiabetic drug metformin are mediated by AMPK. The upstream kinase LKB1 is a tumour suppressor, and AMPK may exert many of its antitumour effects. AMPK activation promotes the oxidative metabolism typical of quiescent cells, rather than the aerobic glycolysis observed in tumour cells and cells involved in inflammation, explaining in part why AMPK activators have both antitumour and anti-inflammatory effects. Salicylate (the major in vivo metabolite of aspirin) activates AMPK, and this could be responsible for at least some of the anticancer and anti-inflammatory effects of aspirin. In addition to metformin and salicylates, novel drugs that modulate AMPK are likely to enter clinical trials soon. Finally, AMPK may be involved in viral infection: downregulation of AMPK during hepatitis C virus infection appears to be essential for efficient viral replication.
Topics: AMP-Activated Protein Kinases; Adenine Nucleotides; Calcium Channels; Cardiomyopathy, Hypertrophic; Diabetes Mellitus, Type 2; Energy Metabolism; Humans; Inflammation; Molecular Structure; Mutation; Neoplasms; Virus Diseases
PubMed: 24824502
DOI: 10.1111/joim.12268