Novel SQSTM1 (c.838G>T) Mutation Identified in Two Unrelated Cases of Cerebellar Ataxia and Gaze Palsy

Mutations in the <i>SQSTM1</i> gene have recently been identified as rare causes of progressive childhood neurodegenerative diseases. To date, only 27 cases have been reported, with 11 different mutations affecting <i>SQSTM1</i>. Here, we describe two new cases of progressive childhood-onset cerebellar ataxia with gaze palsy, in whom clinical exome sequencing identified a novel pathogenic variant. The first patient was a 12-year-old boy of Iraqi and Iranian descent, who presented with a 3-year history of recurrent falls, swaying while walking, and difficulties with writing and speech. Physical examination revealed frozen eye movements, gait ataxia, and dysarthria. The second patient was a 9-year-old Iranian boy, who developed involuntary movements, gait instability, and tremor at the age of 8 years. On examination, cerebellar ataxia and dysarthria were observed. In both cases, initial workup was unremarkable, but whole-exome sequencing revealed a novel homozygous pathogenic truncating mutation, <i>SQSTM1</i> (c.838G>T, p. Glu280Ter). During 2 years of follow-up, the second patient developed gaze palsy. This report highlights the importance of considering <i>SQSTM1</i> mutations in the differential diagnosis of patients presenting with both cerebellar ataxia and ophthalmological manifestations.