ARSACS (autosomal recessive spastic ataxia of Charlevoix-Saguenay) is characterized in individuals born in Quebec Province by early-onset (age 12-18 months) difficulty in walking and gait unsteadiness. In individuals with ARSACS born outside the Province of Quebec, onset is often delayed until later childhood and even adulthood. Ataxia, dysarthria, spasticity, extensor plantar reflexes, distal muscle wasting, a distal sensorimotor neuropathy predominant in the legs, and horizontal gaze nystagmus constitute the most frequent progressive neurologic signs. Yellow streaks of hypermyelinated fibers radiate from the edges of the retina. The retinal changes are uncommon in individuals with ARSACS of French, Italian, Tunisian, and Turkish heritage; they are described as less extensive in persons of Japanese descent. Individuals with ARSACS born in the Province of Quebec become wheelchair bound at the average age of 41 years; cognitive skills are preserved in the long term as individuals remain able to perform daily living tasks late into adulthood. Death commonly occurs in the sixth decade.
Neuroimaging reveals atrophy of the superior vermis, with little extension into lateral cerebellar hemispheres. Dentate nuclei and pontine structures are spared. SACS is the only gene associated with ARSACS. About 96% of individuals with ARSACS from northeastern Quebec are homozygotes or compound heterozygotes for two founder mutations. Molecular genetic testing for these mutations is available on a clinical basis. Molecular genetic testing for mutations observed in other populations is available on a research basis only.
ARSACS is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being neither affected nor a carrier. Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3. Prenatal testing for pregnancies at increased risk is possible if both disease-causing alleles of an affected family member have been identified.