title: Downbeat positioning nystagmus is a common clinical feature despite variable phenotypes in an FHM1 family.
abstract: Clinical examinations and mutational analyses were carried out in three patients of a Japanese familial hemiplegic migraine (FHM) pedigree. Each affected member demonstrated a broad clinical spectrum that included hemiplegic migraine with progressive cerebellar ataxia, migraine without aura, and episodic ataxia. Despite this variability, all members exhibited marked downbeat positioning nystagmus, and magnetic resonance images (MRI) all showed cerebellar atrophy predominantly of the cerebellar vermis. All affected members had a T666M missense mutation in the protein encoded by the CACNA1A gene (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit). Although clinical features associated with the T666M CACNA1A mutation are highly variable, downbeat positioning nystagmus may be an important clinical feature of this disease.
authors.affiliation: Department of Neurology, Hokkaido University Graduate School of Medicine, N15 W7 Kita-ku, Sapporo 060-8638, Japan. yabe@med.hokudai.ac.jp
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yabe
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Yashio
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Keishi
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Takahito
authors.initials: T
authors.lastname: Wada
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsubuku
authors.forename: Norihito
authors.initials: N
authors.lastname: Takeichi
authors.forename: Ken
authors.initials: K
authors.lastname: Sakushima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Soma
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tsuji
authors.forename: Masaaki
authors.initials: M
authors.lastname: Niino
authors.forename: Shinji
authors.initials: S
authors.lastname: Saitoh
authors.forename: Hidenao
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000368:Aged; D001259:Ataxia; D001284:Atrophy; D001921:Brain / Q000473:pathology; D015220:Calcium Channels / Q000235:genetics*; D002524:Cerebellar Ataxia; D002525:Cerebellar Cortex / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020325:Migraine with Aura / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D020326:Migraine without Aura; D020125:Mutation, Missense; D009759:Nystagmus, Pathologic / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D020864:Calcium Channels, N-Type
chemical_list: D015220:Calcium Channels; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type