Episodic Ataxia Type 1 with Distal Weakness: A Novel Manifestation of a Potassium Channelopathy

Abstract

Episodic ataxia type1 (EA1) is an autosomal dominant disorder characterised by episodes of ataxia, dysarthria, tremor and visual disturbances lasting for seconds or minutes, precipitated by physical and emotional stress, startle or sudden movements. In addition there is continuous myokymia. Phenotypic variants such as the combination with epilepsy, shortening of the Achilles tendon in children, transient postural abnormalities in infancy, and a very few patients with longer lasting episodes have been reported. We describe a 10-year-old girl with EA1 who has distal weakness with paresis of the extensors of the feet and prolonged spells of limb stiffness (neuromyotonia) lasting up to 12 hours. A novel single nucleotide change at position 785 T > C that alters a highly conserved residue in the third transmembrane segment of the voltage-gated potassium channel Kv1.1 was found.

Episodic ataxia type 1 - muscle weakness - myokymia - potassium channel Kv1.1 - prolonged attacks

References

• 1 Browne D L, Gancher S T, Nutt J G, Brunt E R, Smith E A, Kramer P, Litt M. Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene KCNA1.  Nat Genet. 1994;  8 136-140
• 2 Brunt E R, Van Weerden T W. Familial paroxysmal kinesigenic ataxia and continuous myokymia.  Brain. 1990;  113 1361-1382
• 3 Eunson L H, Rea R, Zuberi S M, Youroukos S, Panayiotopoulos C P, Liguori R. et al . Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability.  Ann Neurol. 2000;  48 647-656
• 4 Gutmann L, Libell D, Gutmann L. When is myokymia neuromyotonia?.  Muscle & Nerve. 2001;  24 151-153
• 5 Hanson P A, Martinez L B, Cassidy R. Contractures, continuous muscle discharges and titubation.  Ann Neurol. 1977;  1 120-124
• 6 Hart I K, Maddison P, Newsom-Davis J, Vincent A, Mills K R. Phenotypic variants of autoimmune peripheral nerve hyperexcitability.  Brain. 2002;  125 1887-1895
• 7 Jamieson P W, Katirij M B. Idiopathic generalized myokymia.  Muscle & Nerve. 1994;  17 42-51
• 8 Papazian D M, Silverman W R, Lin M C, Tiwari-Woodruff S K, Tang C Y. Structural organisation of the voltage sensor in voltage-dependent potassium channels.  Novartis Found Symp. 2002;  245 178-190
• 9 Rea R, Spauschus A, Eunson L H, Hanna M G, Kullmann D M. Variable K⁺ channel subunit dysfunction in inherited mutations of KCNA1.  J Physiol. 2002;  538 5-23
• 10 Zuberi S M, Eunson L H, Spauschus A, De Silva R, Tolmie J, Wood N W. et al . A novel mutation in the human voltage-gated potassium channel gene (Kv1. 1) associates with episodic ataxia type 1 and sometimes with partial epilepsy.  Brain. 1999;  122 817-825