title: Congenital fibrosis of the extraocular muscles (CFEOM) syndrome associated with progressive cerebellar ataxia.
abstract: We here report on a Japanese family with congenital fibrosis of the extraocular muscles (CFEOM) syndrome associated with slowly progressive cerebellar ataxia. The pedigree indicated autosomal dominant inheritance. All affected individuals showed a complete loss of upgaze function with ptosis, and severe or moderate restriction of downgaze function probably from the birth. Horizontal gaze function was well preserved, except for the eldest patient, who showed both eyes almost totally fixed in exotrophic position. The primary vertical and horizontal position of each eye varied from patient to patient. Aberrant eye movements were observed on attempted upgaze. They showed amblyopia and/or astigmatism, but none of them complained of diplopia. Pupillary reactions were normal, and retinal pigmentary degeneration or optic atrophy was not observed. These ophthalmological findings were consistent with the CFEOM phenotype. The two middle-aged patients, but not the two younger patients, showed slowly progressive gait ataxia with juvenile onset. Magnetic resonance images of the brain indicated cerebellar atrophy in addition to congenital hypoplasia in the cerebellar vermis. Molecular genetic analysis provided a negative linkage to the FEOM3 locus. Linkage to the FEOM1 locus could not be excluded in our family, but mutation in KIF21A, a major cause of the CFEOM1 phenotype, was not detected. We consider that this family may broaden the spectrum of the clinical features of CFEOM or the related disorders presenting with the CFEOM phenotype.
authors.affiliation: Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. kyoshida@hsp.md.shinshu-u.ac.jp
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yoshida
authors.forename: Tomomi
authors.initials: T
authors.lastname: Okano
authors.forename: Kenichi
authors.initials: K
authors.lastname: Hoshi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yahikozawa
authors.forename: Kayo
authors.initials: K
authors.lastname: Suzuki
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Banno
authors.forename: Takuya
authors.initials: T
authors.lastname: Tamura
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Ikeda
mesh_terms: D000293:Adolescent; D000328:Adult; D002524:Cerebellar Ataxia / Q000235:genetics* / Q000473:pathology; D015785:Eye Diseases, Hereditary / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005355:Fibrosis; D008040:Genetic Linkage; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009801:Oculomotor Muscles / Q000473:pathology*; D010375:Pedigree
chemical_list: C119023:KIF21A protein, human; D009419:Nerve Tissue Proteins; D016547:Kinesins