To report a patient with a mutation typically associated with familial amyotrophic lateral sclerosis (ALS), but instead presenting with the corticobasal syndrome (CBS) phenotype.

CBS is defined by atypical parkinsonism and specific examination findings indicating cortical dysfunction. In contrast, corticobasal degeneration (CBD) is a pathological entity and is the principal pathology underlying CBS. CBD and frontotemporal dementia (FTD) often involve tau deposition, but in different topographical distributions, and also in different molecular forms. Many cases of CBD and FTD may, in addition, overlap clinically. By comparison, there is significantly less clinical overlap between ALS and the pathologies that cause CBS. Here we report a case of CBS linked to a mutation in the OPTN gene. This individual has several close relatives diagnosed with familial ALS who also have been found to carry the same OPTN mutation.

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We report a 49-year-old man with 6 months of involuntary movements of the right upper extremity, followed by gait unsteadiness and memory changes. Family history was notable for two siblings with ALS linked to a mutation in the OPTN gene. On exam, we noted right hemidystonia, as well as bradykinesia and brisk reflexes in the right arm. There was gait ataxia, as well as right-sided astereognosis, agraphesthesia, tactile extinction, and ideomotor apraxia. No ocular abnormalities, orthostasis, or other upper-motor neuron features were seen. MRI showed left peri-Rolandic fissure atrophy. Gene testing revealed homozygosity for a loss of function splice-site mutation in the OPTN gene.

This case illustrates differential effects of the same gene mutation in different family members. It is interesting that the pathology causing CBS in this patient shares the same mutation with an inherited form of ALS. The heterogeneity of OPTN phenotypes may be a consequence of the same neuropathology, but with differential topographical distribution in the nervous system.