Beyond dystonia and ataxia: Expanding the phenotype of SQSTM1 mutations

Abstract Background Homozygous sequestomosome-1 gene mutations have been recently linked to neurodegeneration with dystonia, ataxia and gaze palsy. Seven affected families were identified thus far. Objective To describe four new cases with additional phenotypical features. Results Four affected patients from two unrelated families were identified. Two compound heterozygous variants of the gene (c.257_259delins35 and c.301+1G > T) were found in one family (cases 1 and 2), and homozygous c.823_824delAG variant was identified in cases 3 and 4. In addition to the previously described syndrome characterized by cerebellar ataxia, dystonia, choreoathetosis, cognitive impairment and gaze palsy, two subjects presented with iridoplegia. Furthermore, we report dysautonomic features such as orthostatic hypotension and sudomotor dysfunction, along with other non-motor symptoms. Conclusions We expand the phenotype of dystonia caused by Sequestomosome-1 gene by identifying dysautonomic features along with other non-motor symptoms.