title: Expanding the phenotype of potassium channelopathy: severe neuromyotonia and skeletal deformities without prominent Episodic Ataxia.
abstract: We report an unusual family in which the same point mutation in the voltage-gated potassium channel gene KCNA1 resulted in markedly different clinical phenotypes. The propositus presented in infancy with marked muscle stiffness, motor developmental delay, short stature, skeletal deformities, muscle hypertrophy and muscle rippling on percussion. He did not experience episodic ataxia. His mother presented some years later with typical features of Episodic Ataxia type 1 (EA1), with episodes of ataxia lasting a few minutes provoked by exercise. On examination she had myokymia, joint contractures and mild skeletal deformities. A heterozygous point mutation in the voltage-gated K(+) channel (KCNA1) gene (ACG-AGG, Thr226Arg) was found in both. We conclude that mutations in the potassium channel gene (KCNA1) can cause severe neuromyotonia resulting in marked skeletal deformities even if episodic ataxia is not prominent.
authors.affiliation: Dubowitz Neuromuscular Centre, Hammersmith Hospital, Imperial College School of Medicine, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Kinali
authors.forename: H
authors.initials: H
authors.lastname: Jungbluth
authors.forename: L H
authors.initials: LH
authors.lastname: Eunson
authors.forename: C A
authors.initials: CA
authors.lastname: Sewry
authors.forename: A Y
authors.initials: AY
authors.lastname: Manzur
authors.forename: E
authors.initials: E
authors.lastname: Mercuri
authors.forename: M G
authors.initials: MG
authors.lastname: Hanna
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000328:Adult; D001120:Arginine / Q000235:genetics; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D006652:Histological Techniques / Q000379:methods; D006801:Humans; D020386:Isaacs Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D051662:Kv1.1 Potassium Channel; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009154:Mutation; D009243:NAD / Q000378:metabolism; D010641:Phenotype; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D013912:Threonine / Q000235:genetics
chemical_list: C496946:KCNA1 protein, human; D024642:Potassium Channels, Voltage-Gated; D009243:NAD; D051662:Kv1.1 Potassium Channel; D013912:Threonine; D001120:Arginine