Introduction 1 2 3 4 5 3 6 3 4 7 10 11 In the present study, we describe the clinical and genetic features of a new family with hereditary myokymia lacking epilepsy or episodic ataxia. Molecular studies of KCNA1 in the proband revealed a c.676C>A transversion resulting in the substitution of Lys for Thr at codon 226 (T226K) and a c.1355A>C transversion resulting in Y452S. Further genetic studies showed that all affected family members carried the T226K mutation, which was absent in unaffected family members and ethnically matched normal controls, whereas the Y452S substitution was present in both affected and unaffected family members and normal controls. In transfected mammalian cells, electrophysiologic studies demonstrated functional effects of the c.676C>A transversion with no currents above background levels recorded from oocytes injected with the mutant subunit. Co-injection of the wild-type and mutant cRNAs produced significantly smaller whole-oocyte currents than injection with the WT cRNA alone. Materials and methods Clinical data 1 Fig. 1 Squares circles Blackened symbols  Subject II-1 The proband, a 13-year-old boy (II-1), was the product of an unremarkable pregnancy and delivery. He was diagnosed with cerebral palsy because of leg stiffness and delayed walking at 18 months old. Cognitive development was normal; his medical history was significant for esotropia. At 4 years old, he was hospitalized with increasing leg pain, stiffness, and inability to walk during the course of a flu-like illness. Creatine kinase (CK) was elevated at 520 U/l acutely (normal <195 U/l), but was normal when repeated interictally. Examination showed periorbital myokymia, mild abdominal and leg muscle hypertrophy, leg stiffness, spastic gait, hyperreflexia, and bilateral Babinski sign. Magnetic resonance imaging (MRI) of the brain and spine were normal. Metabolic studies including electrolytes, amino and organic acids, carnitine, ammonia, lactate, and thyroid functions were normal. Routine studies of cerebral spinal fluid and an electroencephalogram were normal. Needle EMG of deltoid and iliopsoas muscles showed irregular, polyphasic continuous motor unit discharges with normal interference pattern. Additional family members 1 Molecular studies 2 Dde Dde Oocyte expression and electrophysiological studies Kpn Hin Xenopus laevis 2 2 Results Mutation analysis of KCNA1 Dde 2 Fig. 2 top bottom  Electrophysiological studies of the human Kv1.1 mutant Xenopus 3 3 Fig. 3 Xenopus a c a b c Scale bar d a c a c P  Discussion 6 12 4 7 10 13 14 15 3 Drosophila melanogaster 6 16 16 17