Objective:

To report a rare case of cerebellar syndrome associated with a pathogenic SOD1 variant.

Background:

Pathogenic variants in the SOD1 gene are the second most common cause of genetic amyotrophic lateral sclerosis (ALS). While SOD1-related ALS nearly always manifests with motor neuron features, cerebellar involvement has been rarely described.

Design/Methods:

Clinical and genetic feaatures of patient with cerebellar syndrome was described.

Results:

A 45-year-old woman presented with a one-year history of progressive imbalance and a four-month history of hand clumsiness and mild dysarthria. Her parents were consanguineous, and family history was absent for neurological disease. Neurological examination revealed cerebellar dysarthria, truncal and appendicular ataxia, hyperreflexia, and bilateral Babinski sign without muscle weakness. Electromyography showed no lower motor neuron involvement. Brain MRI demonstrated mild vermian atrophy, and cerebrospinal fluid analysis was normal. Evaluation for acquired ataxia causes, including anti-GAD antibodies, vitamin E level, paraneoplastic autoantibody panel, and malignancy screening, was unremarkable. Whole-exome sequencing identified a homozygous SOD1 Asp91Ala pathogenic variant. The patient’s asymptomatic parents and sister were heterozygous for the variant.

Conclusions:

Pathogenic SOD1 variants may rarely present with isolated cerebellar features, expanding the known clinical spectrum beyond classic ALS. Awareness of such atypical presentations is essential, as SOD1-related motor neuron disease is potentially treatable, and early recognition can have important prognostic and therapeutic implications. Recognition of atypical phenotypes is crucial for early diagnosis and treatment.