A 42-year-old male was referred for evaluation of tremor with onset in adolescence, initially manifesting as postural and kinetic tremor of upper extremities. These evolved into head bobbing and sustained rightward cervical deviation, consistent with cervical dystonia. These coarse movements rendered fine motor function severely impaired, necessitating adaptive methods for feeding, grooming, and other activities of daily living. Additionally endorsed speech issues, and neuropsychological assessment revealed learning deficits in reading and writing, despite normal milestones in early childhood. Family history was significant for two brothers with mucopolysaccharidosis type II (Hunter syndrome), both deceased in early adulthood, and mother with left hemifacial spasm responsive to botulinum toxin.

Neurological examination demonstrated choreiform movements of the bilateral upper extremities in addition to the aforementioned symptoms which were validated on electrophysiological studies as well. Genetic testing for Huntington’s disease was negative, followed by trio-based whole-exome sequencing that identified a pathogenic KMT2B frameshift variant (c.5230_5233del; p.Ser1744IlefsTer150), consistent with autosomal dominant dystonia 28, which accounts for the patient’s complex dystonic and hyperkinetic phenotype. Additionally, a pathogenic FGF14 repeat expansion (290–317/70 repeats) was detected, consistent with autosomal dominant spinocerebellar ataxia type 27B, though this is typically a late-onset, low-penetrance finding. Symptomatic treatment with aripiprazole improved choreiform movements, and botulinum toxin injections were effective for cervical dystonia. 

This case broadens the phenotypic spectrum of KMT2B-related dystonia by highlighting the presence of choreiform movements - a feature reported in only ~2% of cases. The co-occurrence of an FGF14 repeat expansion and familial Hunter syndrome in the same pedigree illustrates the impact of three distinct genetic mechanisms: epigenetic dysregulation (KMT2B), ion channel dysfunction (FGF14), and lysosomal storage pathology (Hunter syndrome). Together, they exemplify how diverse molecular pathways can converge to produce complex neurological phenotypes within a single family.