Objective: To determine the genetic etiology in 2 consanguineous families who presented a novel phenotype of autosomal recessive juvenile amyotrophic lateral sclerosis associated with generalized dystonia.
Methods: A combination of homozygosity mapping and whole-exome sequencing in the first family and Sanger sequencing of candidate genes in the second family were used.
Results: Both families were found to have homozygous loss-of-function mutations in the amyotrophic lateral sclerosis 2 (juvenile) (ALS2) gene.
Conclusions: We report generalized dystonia and cerebellar signs in association with ALS2-related disease. We suggest that the ALS2 gene should be screened for mutations in patients who present with a similar phenotype.