andersen syndrome


Summary: A form of inherited long QT syndrome (or LQT7) that is characterized by a triad of potassium-sensitive periodic paralysis, VENTRICULAR ECTOPIC BEATS, and abnormal features such as short stature, low-set ears, and SCOLIOSIS. It results from mutations of KCNJ2 gene which encodes a channel protein (INWARD RECTIFIER POTASSIUM CHANNELS) that regulates resting membrane potential.

Top Publications

  1. Decher N, Renigunta V, Zuzarte M, Soom M, Heinemann S, Timothy K, et al. Impaired interaction between the slide helix and the C-terminus of Kir2.1: a novel mechanism of Andersen syndrome. Cardiovasc Res. 2007;75:748-57 pubmed
    b>Andersen syndrome (AS) is a rare genetic disease caused by mutations of the potassium channel Kir2.1 (KCNJ2). We identified two unrelated patients with mutations in the slide helix of Kir2.1 leading to AS...
  2. Tristani Firouzi M, Etheridge S. Kir 2.1 channelopathies: the Andersen-Tawil syndrome. Pflugers Arch. 2010;460:289-94 pubmed publisher
    ..Thus, ATS is a disorder of cardiac repolarization. The chapter will discuss the most recent data concerning the genetic, cellular, and clinical data underlying this unique disorder. ..
  3. Ballester L, Benson D, Wong B, Law I, Mathews K, Vanoye C, et al. Trafficking-competent and trafficking-defective KCNJ2 mutations in Andersen syndrome. Hum Mutat. 2006;27:388 pubmed
    ..1, have been identified in Andersen syndrome (or Andersen-Tawil syndrome), an inherited disorder characterized by periodic paralysis, cardiac arrhythmias,..
  4. Rajakulendran S, Tan S, Hanna M. Muscle weakness, palpitations and a small chin: the Andersen-Tawil syndrome. Pract Neurol. 2010;10:227-31 pubmed publisher
    ..Mutations in a potassium channel gene, KCNJ2 which encodes the potassium channel, Kir2.1, underlie the disorder. Here, the authors describe a patient and review the clinical spectrum and genetic features of the disorder...
  5. Tsuboi M, Antzelevitch C. Cellular basis for electrocardiographic and arrhythmic manifestations of Andersen-Tawil syndrome (LQT7). Heart Rhythm. 2006;3:328-35 pubmed
    ..Andersen-Tawil syndrome, a skeletal muscle syndrome associated with periodic paralysis and long QT intervals on the ECG, has been linked to defects in KCNJ2, the gene encoding for the inward rectifier potassium channel (I(K1).)..
  6. Barajas Martinez H, Hu D, Ontiveros G, Caceres G, Desai M, Burashnikov E, et al. Biophysical and molecular characterization of a novel de novo KCNJ2 mutation associated with Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia mimicry. Circ Cardiovasc Genet. 2011;4:51-7 pubmed publisher
    ..The R260P mutation produces a strong dominant negative effect leading to marked suppression of IK1 secondary to a trafficking defect. ..
  7. Zhang L, Benson D, Tristani Firouzi M, Ptacek L, Tawil R, Schwartz P, et al. Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations: characteristic T-U-wave patterns predict the KCNJ2 genotype. Circulation. 2005;111:2720-6 pubmed
    ..The normal QTc, distinct ECG, and other clinical features distinguish ATS1 from long-QT syndrome, and it is best designated as ATS1 rather than LQT7. ..
  8. Marquez M, Totomoch Serra A, Burgoa J, Méndez A, Gómez Flores J, Nava S, et al. Abnormal electroencephalogram, epileptic seizures, structural congenital heart disease and aborted sudden cardiac death in Andersen-Tawil syndrome. Int J Cardiol. 2015;180:206-9 pubmed publisher
  9. Radwański P, Veeraraghavan R, Poelzing S. Cytosolic calcium accumulation and delayed repolarization associated with ventricular arrhythmias in a guinea pig model of Andersen-Tawil syndrome. Heart Rhythm. 2010;7:1428-1435.e1 pubmed publisher
    ..Therefore, therapies aimed at reducing [Ca(2+)](i) rather than APD gradients may prove effective in treatment of ATS1. ..

More Information


  1. Seemann G, Sachse F, Weiss D, Ptacek L, Tristani Firouzi M. Modeling of IK1 mutations in human left ventricular myocytes and tissue. Am J Physiol Heart Circ Physiol. 2007;292:H549-59 pubmed
    ..Thus our modeling approach faithfully recapitulates several features of ATS and provides a mechanistic explanation for the low frequency of torsade de pointes arrhythmia in ATS. ..
  2. Radwański P, Poelzing S. NCX is an important determinant for premature ventricular activity in a drug-induced model of Andersen-Tawil syndrome. Cardiovasc Res. 2011;92:57-66 pubmed publisher
    ..PVA preferentially occurs in regions of enhanced NCX expression with relatively slower Ca(2+) uptake and during perfusion of CPA which further reduces sarcoplasmic reticular Ca(2+) uptake. ..
  3. Gross G. IK1: the long and the short QT of it. Heart Rhythm. 2006;3:336-8 pubmed
  4. Seebohm G, Strutz Seebohm N, Ursu O, Preisig Müller R, Zuzarte M, Hill E, et al. Altered stress stimulation of inward rectifier potassium channels in Andersen-Tawil syndrome. FASEB J. 2012;26:513-22 pubmed publisher
    ..1 genotype. Thus, our findings provide a possible explanation for the contradictory effects of glucocorticoid treatment on symptoms in patients with ATS and may open new pathways for the design of personalized medicines in ATS therapy. ..
  5. Kokunai Y, Nakata T, Furuta M, Sakata S, Kimura H, Aiba T, et al. A Kir3.4 mutation causes Andersen-Tawil syndrome by an inhibitory effect on Kir2.1. Neurology. 2014;82:1058-64 pubmed publisher
    ..4. We propose that KCNJ5 is a second gene causing Andersen-Tawil syndrome. The inhibitory effects of mutant Kir3.4 on inwardly rectifying potassium channels may account for the clinical presentation in both skeletal and heart muscles. ..
  6. Nagase S, Kusano K, Yoshida M, Ohe T. Electrophysiologic characteristics of an Andersen syndrome patient with KCNJ2 mutation. Heart Rhythm. 2007;4:512-5 pubmed
    We report the first case of a patient with Andersen syndrome in whom electrophysiologic study was performed...
  7. Doi T, Makiyama T, Morimoto T, Haruna Y, Tsuji K, Ohno S, et al. A novel KCNJ2 nonsense mutation, S369X, impedes trafficking and causes a limited form of Andersen-Tawil syndrome. Circ Cardiovasc Genet. 2011;4:253-60 pubmed publisher
    ..This alleviation may explain why our patient presented with a relatively mild ATS phenotype. ..
  8. Tan S, Z Graggen W, Boerio D, Rayan D, Howard R, Hanna M, et al. Membrane dysfunction in Andersen-Tawil syndrome assessed by velocity recovery cycles. Muscle Nerve. 2012;46:193-203 pubmed publisher
    ..MVRCs combined with repetitive stimulation differentiated ATS patients from controls more effectively than the conventional long-exercise test. ..
  9. Tani Y, Miura D, Kurokawa J, Nakamura K, Ouchida M, Shimizu K, et al. T75M-KCNJ2 mutation causing Andersen-Tawil syndrome enhances inward rectification by changing Mg2+ sensitivity. J Mol Cell Cardiol. 2007;43:187-96 pubmed
    ..e., increased sensitivity to intracellular Mg2+ and resultant enhancement of inward rectification. The data presented suggest that the mutation may influence clinical features, but it does not directly show this. ..
  10. Kukla P, Biernacka E, Baranchuk A, Jastrzebski M, Jagodzinska M. Electrocardiogram in Andersen-Tawil syndrome. New electrocardiographic criteria for diagnosis of type-1 Andersen-Tawil syndrome. Curr Cardiol Rev. 2014;10:222-8 pubmed
    ..Special attention is paid on the repolarization abnormalities, QT interval and the pathologic U wave. In this article, we aim to provide five new electrocardiographic clues for the diagnosis of ATS1. ..
  11. Sumitomo N, Shimizu W, Taniguchi K, Hiraoka M. Calcium channel blocker and adenosine triphosphate terminate bidirectional ventricular tachycardia in a patient with Andersen-Tawil syndrome. Heart Rhythm. 2008;5:498-9 pubmed publisher
  12. Kim J, Chung K. Novel de novo mutation in the KCNJ2 gene in a patient with Andersen-Tawil syndrome. Pediatr Neurol. 2009;41:464-6 pubmed publisher
    ..The patient did not respond to acetazolamide, but experienced an improvement of the paralytic symptoms on treatment with a combination of spironolactone, amiloride, and potassium supplements. ..
  13. Vega A, Tester D, Ackerman M, Makielski J. Protein kinase A-dependent biophysical phenotype for V227F-KCNJ2 mutation in catecholaminergic polymorphic ventricular tachycardia. Circ Arrhythm Electrophysiol. 2009;2:540-7 pubmed publisher
  14. Fernlund E, Lundin C, Hertervig E, Kongstad O, Alders M, Platonov P. Novel mutation in the KCNJ2 gene is associated with a malignant arrhythmic phenotype of Andersen-Tawil syndrome. Ann Noninvasive Electrocardiol. 2013;18:471-8 pubmed publisher
  15. Thakkar M, Biswas T, Desle H. Hypokalemic periodic paralysis, facial dysmorphism and ventricular arrhythmia (clinical triad of Andersen-Tawil syndrome). J Assoc Physicians India. 2012;60:56-8 pubmed
    ..We report a case of hypokalemic periodic paralysis with dysmorphic facial features and ventricular arrhythmia resembling Andersen-Tawil syndrome. ..
  16. Subbiah R, Gula L, Skanes A, Krahn A. Andersen-Tawil syndrome: management challenges during pregnancy, labor, and delivery. J Cardiovasc Electrophysiol. 2008;19:987-9 pubmed publisher
    ..Effective management strategies are directed at reducing symptoms, arrhythmia burden and sudden cardiac death. This case illustrates the challenges and approach to management of patients with ATS who are pregnant and undergo childbirth. ..
  17. Lu C, Lin J, Rajawat Y, Jerng H, Rami T, Sanchez X, et al. Functional and clinical characterization of a mutation in KCNJ2 associated with Andersen-Tawil syndrome. J Med Genet. 2006;43:653-9 pubmed
    ..It still preserved the ability to co-assemble and traffic to the cell membrane in mammalian cells. For in vivo studies, the T75R-Tg mice had bidirectional ventricular tachycardia after induction and longer QT intervals. ..
  18. Kuramoto Y, Furukawa Y, Yamada T, Okuyama Y, Fukunami M. Andersen-Tawil syndrome associated with aborted sudden cardiac death: atrial pacing was effective for ventricular arrhythmias. Am J Med Sci. 2012;344:248-50 pubmed publisher
    ..Moreover, increasing the pacing rate significantly decreased them. These findings indicate that the arrhythmia was bradycardia-dependent in this case. ..
  19. Sung R, Wu S, Wu J, Chang H, Luo C. Electrophysiological mechanisms of ventricular arrhythmias in relation to Andersen-Tawil syndrome under conditions of reduced IK1: a simulation study. Am J Physiol Heart Circ Physiol. 2006;291:H2597-605 pubmed
    ..In patients with ATS, the hypokalemic form of periodic paralysis should have the highest propensity to VAs, especially during physical activity. ..
  20. Kamate M, Chetal V. Andersen Tawil syndrome - periodic paralysis with dysmorphism. Indian Pediatr. 2011;48:64-5 pubmed
    ..It is a type of potassium channelopathy that occurs sporadically or by autosomal dominant inheritance. We report a 14 year old boy with Andersen-Tawil syndrome. ..
  21. Chan H, Chen M, Su J, Ko L, Lin C, Wu R. A novel neuropsychiatric phenotype of KCNJ2 mutation in one Taiwanese family with Andersen-Tawil syndrome. J Hum Genet. 2010;55:186-8 pubmed publisher
    ..Patients with ATS, especially those carrying the KCNJ2 mutations, should be monitored for their potential neuropsychiatric system involvement. ..
  22. Schoonderwoerd B, Wiesfeld A, Wilde A, van den Heuvel F, van Tintelen J, van den Berg M, et al. A family with Andersen-Tawil syndrome and dilated cardiomyopathy. Heart Rhythm. 2006;3:1346-50 pubmed
  23. Ballester L, Vanoye C, George A. Exaggerated Mg2+ inhibition of Kir2.1 as a consequence of reduced PIP2 sensitivity in Andersen syndrome. Channels (Austin). 2007;1:209-17 pubmed
    b>Andersen syndrome is an autosomal dominant disorder characterized by cardiac arrhythmias, periodic paralysis and dysmorphic features...
  24. Radwański P, Greer Short A, Poelzing S. Inhibition of Na+ channels ameliorates arrhythmias in a drug-induced model of Andersen-Tawil syndrome. Heart Rhythm. 2013;10:255-63 pubmed publisher
  25. Pegan S, Arrabit C, Slesinger P, Choe S. Andersen's syndrome mutation effects on the structure and assembly of the cytoplasmic domains of Kir2.1. Biochemistry. 2006;45:8599-606 pubmed
    ..Finally, we observed a potassium ion bound to the cytoplasmic domain for this class of K+ channels...
  26. Nagashima M, Higaki T, Seike Y, Yokoyama Y. Cardiac surgery for a patient with Andersen-Tawil syndrome. Ann Thorac Surg. 2010;90:285-7 pubmed publisher
    ..We present a case of successful cardiac surgery in a patient with Andersen-Tawil syndrome, without using cardioplegia. ..
  27. Lim B, Kim G, Bae E, Noh C, Hwang H, Kim K, et al. Andersen cardiodysrhythmic periodic paralysis with KCNJ2 mutations: a novel mutation in the pore selectivity filter residue. J Child Neurol. 2010;25:490-3 pubmed publisher
    ..Intermittent muscle weakness in childhood warrants careful evaluation of cardiac dysrhythmia and skeletal anomalies. ..
  28. Tristani Firouzi M. Andersen-Tawil syndrome: an ever-expanding phenotype?. Heart Rhythm. 2006;3:1351-2 pubmed
  29. Peters S, Schulze Bahr E, Etheridge S, Tristani Firouzi M. Sudden cardiac death in Andersen-Tawil syndrome. Europace. 2007;9:162-6 pubmed
    ..Although ventricular tachycardia burden is quite high sudden cardiac death in ATS is rare. We describe a case with sudden cardiac death due to electrical storm a few days after ICD implantation in KCNJ2 mutation-negative ATS. ..
  30. Sansone V, Tawil R. Management and treatment of Andersen-Tawil syndrome (ATS). Neurotherapeutics. 2007;4:233-7 pubmed
    ..We review the clinical, laboratory, and genetic features of this disorder with particular emphasis on treatment and management. ..
  31. Hehir M, Logigian E. Electrodiagnosis of myotonic disorders. Phys Med Rehabil Clin N Am. 2013;24:209-20 pubmed publisher
    ..This article reviews myotonia and its differential diagnosis. The use of electrodiagnostic testing to evaluate the primary myotonic disorders (myotonic dystrophy and the nondystrophic myotonias) is also discussed. ..
  32. Sacconi S, Simkin D, Arrighi N, Chapon F, Larroque M, Vicart S, et al. Mechanisms underlying Andersen's syndrome pathology in skeletal muscle are revealed in human myotubes. Am J Physiol Cell Physiol. 2009;297:C876-85 pubmed publisher
    ..Our data describe for the first time the functional consequences of Andersen's syndrome mutations ex vivo and provide clues to the K+ channel pathophysiology in skeletal muscle. ..
  33. Choi B, Kim J, Suh B, Yu J, Sunwoo I, Kim S, et al. Mutations of KCNJ2 gene associated with Andersen-Tawil syndrome in Korean families. J Hum Genet. 2007;52:280-3 pubmed
    ..The M307I mutation is a novel mutation, located at the intracellular C-terminal domain, which is known to be concerned with putative phosphatidylinositol 4,5-bisphosphate (PIP(2)) binding and channel trafficking. ..
  34. Ma D, Taneja T, Hagen B, Kim B, Ortega B, Lederer W, et al. Golgi export of the Kir2.1 channel is driven by a trafficking signal located within its tertiary structure. Cell. 2011;145:1102-15 pubmed publisher
    ..1 reveals a quality control step that couples protein conformation to Golgi export and provides molecular insight into how mutations in Kir2.1 arrest the channels at the Golgi. ..
  35. Marrus S, Cuculich P, Wang W, Nerbonne J. Characterization of a novel, dominant negative KCNJ2 mutation associated with Andersen-Tawil syndrome. Channels (Austin). 2011;5:500-9 pubmed publisher
    ..1-D71Y mutant protein functions as a dominant negative subunit resulting in reduced inwardly rectifying K(+) current amplitudes and altered cellular excitability in patients with Andersen-Tawil syndrome. ..
  36. Bichet D, Duranton C, Hirbec H, Kellenberger S, Merot J, Ulmann L, et al. The 19th Ion Channel Meeting. September 2008, France. Channels (Austin). 2009;3:69-72 pubmed
    ..The meeting is an opportunity for leading investigators as well as young researchers to present and discuss their recent advances and future challenges in the ion channel field. ..
  37. Tengan C, Antunes A, Bauab J, Baubab J, Prado G, Manzano G, et al. Andersen syndrome: an association of periodic paralysis, cardiac arrhythmia and dysmorphic abnormalities. Arq Neuropsiquiatr. 2006;64:582-4 pubmed
    b>Andersen syndrome (AS) is a rare disease characterized by the presence of periodic paralysis (PP), cardiac arrhythmia and dysmorphic abnormalities...
  38. Erdogan O, Aksoy A, Turgut N, Durusoy E, Samsa M, Altun A. Oral verapamil effectively suppressed complex ventricular arrhythmias and unmasked U waves in a patient with Andersen-Tawil syndrome. J Electrocardiol. 2008;41:325-8 pubmed publisher
    ..We present a case of an elderly patient with ATS whose symptomatic ventricular arrhythmias including BVT were effectively suppressed by oral verapamil therapy. ..
  39. Modoni A, Bianchi M, Vitulano N, Pagliarani S, Perna F, Sanna T, et al. Lack of any cardiac involvement in a patient with Andersen-Tawil syndrome associated with the c.574A?G mutation in KCNJ2. Cardiology. 2011;120:200-3 pubmed publisher
  40. Yoon G, Quitania L, Kramer J, Fu Y, Miller B, Ptacek L. Andersen-Tawil syndrome: definition of a neurocognitive phenotype. Neurology. 2006;66:1703-10 pubmed
    ..46, 3.21; p = 0.056) and 23.4 points for mathematics (95% CI -42.53, -4.22; p = 0.017). Mutations in KCNJ2 are associated with a distinct neurocognitive phenotype, characterized by deficits in executive function and abstract reasoning. ..
  41. Bokenkamp R, Wilde A, Schalij M, Blom N. Flecainide for recurrent malignant ventricular arrhythmias in two siblings with Andersen-Tawil syndrome. Heart Rhythm. 2007;4:508-11 pubmed
  42. Nguyen H, Pieper G, Wilders R. Andersen-Tawil syndrome: clinical and molecular aspects. Int J Cardiol. 2013;170:1-16 pubmed
    ..Thus far, the molecular mechanism of the dysmorphic features is only poorly understood. In this review, we summarize the clinical symptoms, the underlying genetic and molecular defects, and the management and treatment of ATS. ..
  43. Kim N, Jang J, Jeon G, Cho E, Sin J. Identification of the KCNJ2 Mutation in a Korean Family with Andersen-Tawil Syndrome and Developmental Delay. Ann Clin Lab Sci. 2016;46:110-3 pubmed
    ..This report highlights the importance of an exome study for unusual clinical manifestations, such as preand postnatal growth restriction, developmental delay, and the lack of a critical diagnostic clue, such as periodic paralysis. ..
  44. Scheiper S, Hertel B, Beckmann B, Kaab S, Thiel G, Kauferstein S. Characterization of a novel KCNJ2 sequence variant detected in Andersen-Tawil syndrome patients. BMC Med Genet. 2017;18:113 pubmed publisher
    ..The detected sequence variant causes loss-of-function of the Kir2.1 channel and explains the clinical phenotypes observed in Andersen-Tawil syndrome patients. ..
  45. Delannoy E, Sacher F, Maury P, Mabo P, Mansourati J, Magnin I, et al. Cardiac characteristics and long-term outcome in Andersen-Tawil syndrome patients related to KCNJ2 mutation. Europace. 2013;15:1805-11 pubmed publisher
    ..Despite a severe clinical presentation with a very high rate of ventricular arrhythmias, the arrhythmic prognosis of the ATS patients is relatively good under treatment. ..
  46. Pellizzón O, Kalaizich L, Ptacek L, Tristani Firouzi M, Gonzalez M. Flecainide suppresses bidirectional ventricular tachycardia and reverses tachycardia-induced cardiomyopathy in Andersen-Tawil syndrome. J Cardiovasc Electrophysiol. 2008;19:95-7 pubmed
  47. Yoon G, Oberoi S, Tristani Firouzi M, Etheridge S, Quitania L, Kramer J, et al. Andersen-Tawil syndrome: prospective cohort analysis and expansion of the phenotype. Am J Med Genet A. 2006;140:312-21 pubmed
    ..Detailed anthropometric, neurological, and cardiac evaluations were performed. Using this approach, we identified novel skeletal and dental findings and proposed additional diagnostic criteria for ATS dysmorphology. ..
  48. Limberg M, Zumhagen S, Netter M, Coffey A, Grace A, Rogers J, et al. Non dominant-negative KCNJ2 gene mutations leading to Andersen-Tawil syndrome with an isolated cardiac phenotype. Basic Res Cardiol. 2013;108:353 pubmed publisher
    ..1, Kir2.2 and Kir2.3 currents. Thus, a mild reduction of native Kir2.x currents by non dominant-negative mutants may cause ATS with an isolated cardiac phenotype. ..
  49. Jefferies J, Kim J, Belmont J, Friedman R. The Twiddling Andersen. Tex Heart Inst J. 2009;36:349-51 pubmed
    ..Twiddler syndrome is characterized by intentional or inadvertent manipulation of implanted devices in the pacemaker pocket. We describe an unusual case of an 8-year-old girl who had both syndromes. ..
  50. Jedele K. The overlapping spectrum of rett and angelman syndromes: a clinical review. Semin Pediatr Neurol. 2007;14:108-17 pubmed
    ..The reversal of symptoms of Rett syndrome in a mature mouse model suggests the possibility for treatment of these and perhaps other autism-related disorders in the future. ..
  51. Tully I, Atherton J, Hunt L, Ingles J, Semsarian C, McGaughran J. Rarity and phenotypic heterogeneity provide challenges in the diagnosis of Andersen-Tawil syndrome: Two cases presenting with ECGs mimicking catecholaminergic polymorphic ventricular tachycardia (CPVT). Int J Cardiol. 2015;201:473-5 pubmed publisher
  52. Young D. Anesthesia for the child with Andersen's Syndrome. Paediatr Anaesth. 2005;15:1019-20 pubmed
  53. Kimura H, Zhou J, Kawamura M, Itoh H, Mizusawa Y, Ding W, et al. Phenotype variability in patients carrying KCNJ2 mutations. Circ Cardiovasc Genet. 2012;5:344-53 pubmed publisher
    ..KCNJ2 gene screening in atypical ATS phenotypes is of clinical importance because more than half of mutation carriers express atypical phenotypes, despite their arrhythmia severity. ..