title: Costeff syndrome: clinical features and natural history.
abstract: Costeff syndrome (CS) is a rare autosomal-recessive neurological disorder, which is known almost exclusively in patients of Iraqi Jewish descent, manifesting in childhood with optic atrophy, ataxia, chorea and spastic paraparesis. Our aim was to study the clinical spectrum of CS and natural history using a cross-sectional study design. Consecutive patients with CS were recruited to the study. Patients were diagnosed based on clinical features, along with elevated urinary levels of methylglutaconic and methylglutaric acid, and by identification of the disease-causing mutation in the OPA3 gene in most. All patients were examined by a neurologist and signs and symptoms were rated. 28 patients with CS (16 males, 21 families, age at last observation 28.6 ± 16.1 years, range 0.5-68 years) were included. First signs of neurological deficit appeared in infancy or early childhood, with delayed motor milestones, choreiform movements, ataxia and visual disturbances. Ataxia and chorea were the dominant motor features in childhood, but varied in severity among patients and did not seem to worsen with age. Pyramidal dysfunction appeared later and progressed with age (r = 0.71, p < 0.001) leading to spastic paraparesis and marked gait impairment. The course of neurological deterioration was slow and the majority of patients could still walk beyond the fifth decade. While visual acuity seemed to deteriorate, it did not correlate with age. CS is a rare neurogenetic disorder that causes serious disability and worsens with age. Spasticity significantly increases over the years and is the most crucial determinant of neurological dysfunction.
authors.affiliation: Parkinson Disease and Movement Disorders Clinic, Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan, 52621, Israel, gyahalom@gmail.com.
authors.forename: Gilad
authors.initials: G
authors.lastname: Yahalom
authors.forename: Yair
authors.initials: Y
authors.lastname: Anikster
authors.forename: Ruth
authors.initials: R
authors.lastname: Huna-Baron
authors.forename: Chen
authors.initials: C
authors.lastname: Hoffmann
authors.forename: Lubov
authors.initials: L
authors.lastname: Blumkin
authors.forename: Dorit
authors.initials: D
authors.lastname: Lev
authors.forename: Rakefet
authors.initials: R
authors.lastname: Tsabari
authors.forename: Zeev
authors.initials: Z
authors.lastname: Nitsan
authors.forename: Sheera F
authors.initials: SF
authors.lastname: Lerman
authors.forename: Bruria
authors.initials: B
authors.lastname: Ben-Zeev
authors.forename: Ben
authors.initials: B
authors.lastname: Pode-Shakked
authors.forename: Shira
authors.initials: S
authors.lastname: Sofer
authors.forename: Avraham
authors.initials: A
authors.lastname: Schweiger
authors.forename: Tally
authors.initials: T
authors.lastname: Lerman-Sagie
authors.forename: Sharon
authors.initials: S
authors.lastname: Hassin-Baer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002819:Chorea / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology / Q000652:urine; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology / Q000652:urine*; D008875:Middle Aged; D009128:Muscle Spasticity / Q000503:physiopathology*; D009896:Optic Atrophy / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology / Q000652:urine; D011506:Proteins / Q000235:genetics*; D015419:Spastic Paraplegia, Hereditary / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology / Q000652:urine; D055815:Young Adult
chemical_list: C443108:OPA3 protein, human; D011506:Proteins