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.