Andersen-Tawil syndrome (ATS) – Case report and literature review
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Chair and Department of Jaw Orthopaedics, Medical University in Lublin, Poland
Chair and Department of Paediatric Dentistry, Medical University in Lublin, Poland
Katarzyna Olszewska   

Chair and Department of Jaw Orthopaedics, Medical University in Lublin, Poland, Staszica 16, 20–081 Lublin, Poland
J Pre Clin Clin Res. 2014;8(2):123–126
Andersen-Tawil Syndrome (ATS) is a rare genetic disorder inherited in an autosomal dominant pattern caused by mutations in the KCNJ2 gene encoding Kir2.1 protein forming potassium ion channel, leading to disruption of cardiac and skeletal muscle repolarisation. Clinical symptoms include periodic paralysis, ventricular arrhythmia associated with QT prolongation and typical skeletal and facial dysmorphic features. The aim of the study was to present characteristic features of the rare Andersen-Tawil syndrome (ATS) within the face and oral cavity of a 9-year-old boy. The patient was diagnosed with Andersen-Tawil syndrome (OMIM#170390) at the age of 8 due to the positive family history, typical dysmorphic features, and the presence of mutation in the KCNJ2 gene confirmed by genetic testing. Typical manifestations of ATS were diagnosed: cardiac arrhythmia, short stature, scoliosis and clinodactyly. Clinical examination revealed typical facial dysmorphic features of ATS: broad forehead, triangular shape of the face, hypertelorism, microstomia, low-set ears, and mandibular retrognathism. Intraoral examination revealed: high-arched palate, crowding in the dental arches, hypomineralisation of enamel and high incidence of dental caries. Dental age assessment by Demirijan pointed to delayed development of permanent dentition. Cephalometric analysis revealed skeletal class II with high angle vertical jaws relation. Diagnosis of ATS requires high index of suspicion because of a great variability in the clinical manifestation of the syndrome. The subtle nature of the dysmorphic features often delays the diagnosis of this syndrome, and its potentially lethal cardiac arrhythmia remaining undetected.
Klein R, Ganelin R, Marks JF, Usher P, Richards C. Periodic paralysis with cardiac arrhythmia. J Pediatr. 1963; 62: 371–385.
Andersen ED, Krasilnikoff PA, Overvad H. Intermittent muscular weakness, extrasystoles and multiple developmental anomalies. A new syndrome? Acta Paediatr Scand. 1971; 60: 559–564.
Tawil R, Ptacek LJ, Pavlakis SG. Andersen’s syndrome: potassium-sensitive periodic paralysis, ventricular ectopy, and dysmorphic features. Ann Neurol. 1994; 35: 326–330.
Nguyen HL, Pieper GH, Wilders R. Andersen-Tawil syndrome: clinical and molecular aspects. Int J Cardiol. 2013; 170: 1–16.
Sansone V, Griggs RC, Meola G. Andersen’s syndrome: a distinct periodic paralysis. Ann Neurol. 1997; 42: 305–312.
Tristani-Firouzi M, Jensen JL, Donaldson MR. Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). Clin Invest. 2002; 110: 381–388.
Yoon G, Oberoi S, Tristani-Firouzi M. Andersen Tawil syndrome: prospective cohort analysis and expansion of the phenotype. Am J Med Genet A. 2006; 140: 312–321.
Donaldson MR, Yoon G, Fu YH, Ptacek LJ. Andersen Tawil syndrome: a model of clinical variability, pleiotropy, and genetic heterogeneity. Ann Med. 2004; 36 (Suppl. 1): 92–97.
Sansone V, Tawil R. Management and treatment of Andersen-Tawil syndrome (ATS). Neurotherapeutics. 2007; 4: 233–237.
Yoon G, Quitania L, Kramer JH, Fu YH, Miller BL, Ptácek LJ. Andersen Tawil syndrome: definition of a neurocognitive phenotype. Neurology. 2006; 66: 1703–1710.
Plaster NM, Tawil R, Tristani-Firouzi M. Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen’s syndrome. Cell. 2001; 105: 511–519.
Limberg MM, Zumhagen S, Netter MF. Non dominant-negative KCNJ2 gene mutations leading to Andersen-Tawil syndrome with an isolated cardiac phenotype. Basic Res Cardiol. 2013; 108: 353.
Hasegawa K, Ohno S, Kimura H. Mosaic KCNJ2 mutation in Andersen Tawil syndrome: targeted deep sequencing is useful for the detection of mosaicism. Clin Genet. 2014.
Andelfinger G, Tapper AR, Welch RC. KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes. Am J Hum Genet. 2002; 71: 663–668.
Tengan CH, Antunes AC, Bauab JR, Prado GF, Manzano GM, Gabbai AA. Andersen syndrome: an association of periodic paralysis, cardiac arrhythmia and dysmorphic abnormalities. Arq Neuropsiquiatr. 2006; 64: 582–584.
Haruna Y, Kobori A, Makiyama T. Genotype–phenotype correlations of KCNJ2 mutations in Japanese patients with Andersen Tawil syndrome. Hum Mutat. 2007; 28: 208.
Kotulska A, Kucharz EJ. Andersen-Tawil syndrome – a review of the literature and a case report. Reumatologia. 2008; 46(3): 171–174.
Kamate M, Chetal V. Andersen-Tawil syndrome – periodic paralysis with dysmorphism. Ind Pediatr. 2011; 48: 64–65.
Chan HF, Chen ML, Su JJ, Ko LC, Lin CH, Wu RM. A novel neuropsychiatric phenotype of KCNJ2 mutation in one Taiwanese family with Andersen-Tawil syndrome. J Hum Genet. 2010; 55: 186–188.
Barajas-Martinez H, Hu D, Ontiveros G. 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: 51–57.
Thakkar M, Biswas TK, Desle HB. Hypokalemic periodic paralysis, facial dysmorphism and ventricular arrhythmia (clinical triad of Andersen- Tawil syndrome). J Assoc Physician I. 2012; 60: 56–58.
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: 471–478.