PSEUDODOMINANT INHERITANCE OF SPASTIC ATAXIA OF CHARLEVOIX-SAGUENAY

Spastic ataxia of Charlevoix-Saguenay (ARSACS, MIM 270550) is an early-onset neurodegenerative disease characterized by mild to moderate early-onset ataxia, spastic paraparesis, sensory motor neuropathy in the lower limbs, and almost invariably atrophy of the upper cerebellar vermis on brain MRI.1 Autosomal recessively inherited mutations in SACS have been described in several ethnicities and the range of mutations is growing rapidly.2 We report the clinical and molecular characterization of a family with an apparent vertical transmission of spastic ataxia where the pseudodominant transmission was explained by the combination of a large-scale deletion removing SACS with 2 novel nonsense variants. ### Case reports. The family pedigree is outlined in the figure. Patient II-1 is a 42-year-old woman. Early motor milestones were normal, but she was noted to be clumsy at school, with motor deterioration noted from age 16 years. At 24 years, neurologic examination showed cerebellar dysarthria, saccadic intrusions in pursuit eye movements, brisk arm and knee reflexes, absent ankle reflexes, and bilateral Babinski sign. Nerve conduction studies were not performed. A brain MRI scan disclosed thinning of the cervical cord but was otherwise unremarkable. When reassessed at age 34 years, her disability had progressed with an episode of diplopia and relapsing weakness. She had mild urinary urgency, and required a stick to walk. Her cognition was normal. Visual, auditory, and somatosensory evoked potentials showed delayed responses, and CSF examination showed oligoclonal bands. Brain MRI showed periventricular white matter abnormalities and mild cerebellar, brainstem, and cervical cord atrophy (figure, A–C). It was concluded that she had …