Case report Inherited neuromyotonia: A clinical and genetic study of a family Antonio Falace a , Pasquale Striano a,b, * , Fiore Manganelli b , Antonietta Coppola b , Salvatore Striano b , Carlo Minetti a , Federico Zara a a Neuromuscular and Neurodegenerative Disease Unit, University of Genova, ‘‘G. Gaslini Institute’’, Genova, Italy b Department of Neurological Sciences, Federico II University, Naples, Italy Received 7 February 2006; received in revised form 11 September 2006; accepted 20 September 2006 Abstract Neuromyotonia is a disorder of peripheral nerve hyperexcitability characterized by myokymia, muscle cramps and stiffness, delayed muscle relaxation after contraction (pseudomyotonia), and hyperhidrosis, associated with well described spontaneous elec- tromyographic features. It is usually an acquired disorder associated with autoantibodies against neuronal voltage-gated potassium channels. However, mutations of KCNA1, encoding the K + channel subunit hKv1.1, have been reported in rare families with neu- romyotonia, and mutations in KCNQ2, encoding voltage-gated potassium M channel subunit, in families with benign neonatal sei- zures and myokymia. We report a three-generation family with inherited neuromyotonia without evidence of immunological involvement. Genetic study excluded mutations in KCNA1, KCNA2, KCNA6 and KCNQ2 genes. Our study does not completely exclude the involvement of other genes encoding ion channels subunits in the pathogenesis of this disorder. Further studies of famil- ial cases will shed light on the molecular basis of inherited neuromyotonia. Ó 2006 Elsevier B.V. All rights reserved. Keywords: Inherited neuromyotonia; Peripheral nerve hyperexcitability; Isaac’s syndrome; Myokymia; Potassium channelopathies 1. Introduction Neuromyotonia is a disorder of peripheral nerve hyperexcitability characterized by myokymia, muscle cramps and stiffness, delayed muscle relaxation after contraction (pseudomyotonia), and hyperhidrosis, asso- ciated with well described spontaneous electromyo- graphic features [1,2]. Neuromyotonia is usually an acquired immuno-med- iated disorder occurring in isolated form or associated to autoimmune diseases, such as myasthenia gravis [1,2]. Autoantibodies directed against neuronal Shaker-relat- ed voltage-gated potassium channels (VGKCs), encoded by the KCNA1, KCNA2, KCNA6 genes, have been documented in affected patients [1,2]. More rarely, neuromyotonia is inherited, sometimes in association with other clinical features [3–8]. Muta- tions of KCNA1, encoding the K + channel subunit hKv1.1, are found in autosomal dominant episodic ataxia type 1, characterized by neuromyotonia, paroxys- mal ataxia and dysarthria [4–7]. Furthermore, mutations in KCNQ2-encoding a volt- age-gated potassium M channel subunit-have been found in benign familial neonatal seizures and myokymia [8]. Here, we report the clinical and genetic study of a rare family with inherited neuromyotonia without evi- dence of immunological involvement. 2. Patients and methods This three-generation family originates from South- ern Italy (Fig. 1). There is no evidence of consanguinity. The local Ethic Committee approved the study and 0960-8966/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.nmd.2006.09.014 * Corresponding author. Tel.: +39 010 5636603; fax: +39 010 3538265. E-mail address: sstriano@libero.it (P. Striano). www.elsevier.com/locate/nmd Neuromuscular Disorders 17 (2007) 23–27