The G93C mutation in superoxide dismutase 1: clinicopathologic phenotype and prognosis.

Background: Twenty percent of familial amyotrophic lateral sclerosis (ALS) is caused by mutations in the superoxide dismutase 1 gene (SOD1). Few data exist on their clinicopathologic phenotypes.

Objectives: To determine the clinical and pathologic phenotype associated with the G93C mutation in SOD1 and to compare survival in familial ALS related to this mutation with survival in other ALS subgroups.

Design: Retrospective study.

Setting: Tertiary referral center for neuromuscular disorders.

Patients: Twenty patients with the G93C mutation for whom clinical data were available and 1 patient with pathologic data.

Main Outcome Measures: Characteristics and survival compared with other ALS subgroups, adjusting for known prognostic factors.

Results: The G93C mutation was associated with a purely lower motor neuron phenotype without bulbar involvement. Presence of the mutation independently predicted longer survival compared with other ALS subgroups. Pathologic examination showed degeneration of the anterior horn, spinocerebellar tracts, and posterior funiculi, with minimal involvement of corticospinal tracts and no degeneration of brainstem motor nuclei. Survival motor neuron gene copy number had no significant influence on age at onset or survival in patients with the G93C mutation.

Conclusions: These findings add to the knowledge of SOD1-related familial ALS and demonstrate further clinicopathologic variability between different SOD1 mutations. Finally, they demonstrate the independent prognostic value of the G93C mutation.