Mutation in KCNJ2 Gene in a Boy with Atypical Features of Andersen–Tawil Syndrome, ADHD, and ASD: An Expanding Phenotype

Abstract

Andersen–Tawil syndrome, a potassium ion channelopathy, is caused by mutations in the KCNJ2 gene, and accounts for approximately 10% of channelopathies. Phenotype is variable. An 11-year-old boy presented with periodic paralysis without localizing neurological signs, associated in only two of three occasions with hypokalemia, on a background of a diagnosis of attention deficit hyperactivity disorder and autism spectrum disorder. There was a history of syncope and palpitations. This was a matter of diagnostic uncertainty due to the difficulty in interpreting his neurological signs, and inconsistency of abnormal potassium levels. In children/young people with recurrent episodes of weakness without localizing signs on physical examination, and syncope, the possibility of a channelopathy should be considered, even in the absence of serum electrolyte abnormalities. There is a possible link between KCNJ2 mutations and difficulties in attention and a specific neurocognitive profile.

Keywords

KCNJ2 - Andersen–Tawil syndrome - potassium ion channelopathy - hypokalemic periodic paralysis

Publication History

Received: 27 September 2019

Accepted: 16 December 2019

Article published online:
23 February 2020

• References

• 1 Plaster NM, Tawil R, Tristani-Firouzi M. et al. Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell 2001; 105 (04) 511-519
• 2 Sansone V, Tawil R. Management and treatment of Andersen-Tawil syndrome (ATS). Neurotherapeutics 2007; 4 (02) 233-237
• 3 Nguyen HL, Pieper GH, Wilders R. Andersen-Tawil syndrome: clinical and molecular aspects. Int J Cardiol 2013; 170 (01) 1-16
• 4 Andersen ED, Krasilnikoff PA, Overvad H. Intermittent muscular weakness, extrasystoles, and multiple developmental anomalies. A new syndrome?. Acta Paediatr Scand 1971; 60 (05) 559-564
• 5 Raab-Graham KF, Radeke CM, Vandenberg CA. Molecular cloning and expression of a human heart inward rectifier potassium channel. Neuroreport 1994; 5 (18) 2501-2505
• 6 Andelfinger G, Tapper AR, Welch RC, Vanoye CG, George Jr AL, Benson DW. KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes. Am J Hum Genet 2002; 71 (03) 663-668
• 7 Delannoy E, Sacher F, Maury P. et al. Cardiac characteristics and long-term outcome in Andersen-Tawil syndrome patients related to KCNJ2 mutation. Europace 2013; 15 (12) 1805-1811
• 8 Sansone V, Meola G, Links TP, Panzeri M, Rose MR. Treatment for periodic paralysis. Cochrane Database Syst Rev 2008; (01) CD005045
• 9 Yoon G, Oberoi S, Tristani-Firouzi M. et al. Andersen-Tawil syndrome: prospective cohort analysis and expansion of the phenotype. Am J Med Genet A 2006; 140 (04) 312-321
• 10 Tristani-Firouzi M, Jensen JL, Donaldson MR. et al. Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome). J Clin Invest 2002; 110 (03) 381-388
• 11 Sansone V, Griggs RC, Meola G. et al. Andersen's syndrome: a distinct periodic paralysis. Ann Neurol 1997; 42 (03) 305-312
• 12 Yoon G, Quitania L, Kramer JH, Fu YH, Miller BL, Ptácek LJ. Andersen-Tawil syndrome: definition of a neurocognitive phenotype. Neurology 2006; 66 (11) 1703-1710
• 13 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 (03) 186-188