Juvenile Huntington Disease With Cerebellar-Predominant Atrophy Identified by Genome Sequencing

Juvenile Huntington disease accounts for a small fraction of Huntington disease cases and is driven by the largest trinucleotide repeat expansions. We describe a 6-year-old boy with progressive global regression, generalized dystonia, and epilepsy, in whom serial imaging showed striking cerebellar-predominant atrophy with an initially normal-appearing striatum. Extensive metabolic testing, exome sequencing, and an ataxia repeat expansion panel were nondiagnostic. Research genome sequencing identified a large pathogenic huntingtin CAG repeat expansion that confirmatory testing sized beyond 180 repeats. This case illustrates a cerebellar-predominant imaging signature of extreme repeat expansions and the limitations of exome sequencing for detecting them.