Expanding the phenotypic spectrum of THAP1 dystonia: a scoping review with an illustrative case of late-onset focal limb dystonia.

THAP1-associated dystonia (DYT-THAP1) is classically described as an early-onset disorder with craniocervical involvement and potential for generalization. However, increasing reports suggest a broader phenotypic spectrum, including adult-onset presentations. We aimed to characterize the clinical phenotype of genetically confirmed DYT-THAP1 with age at onset ≥ 40 years, and to highlight an illustrative case. A scoping review was conducted following Joanna Briggs Institute methodology. Comprehensive searches of PubMed, MDSGene, Google Scholar, and regional databases identified studies reporting patient-level clinical data in individuals with genetically confirmed THAP1 mutations and late-onset disease. Data on age of onset, site of onset, distribution, sex, family history, mutation geste antagoniste were extracted and synthesized descriptively. Twenty-two studies comprising 50 patients met the set inclusion criteria. Cranial dystonia was the most common site of onset (n = 22), followed by cervical (n = 13), while limb onset was uncommon. Most patients presented with segmental distribution (n = 27), followed by focal (n = 20), and only 3 cases demonstrated generalized involvement. The majority of cases were sporadic (37/50). Associated clinical features and geste antagoniste were infrequently and inconsistently reported across studies. We additionally present a Filipina with late-onset focal lower limb dystonia, further highlighting an atypical pattern of limb onset. Collectively, these findings suggest that late-onset THAP1-associated dystonia may exhibit a phenotype distinct from classical early-onset presentations characterized by cranial and cervical predominance, segmental distribution, and frequent sporadic occurrence. Recognition of this broader phenotypic spectrum may facilitate consideration of genetic etiologies in adult-onset dystonia, even in the absence of a family history.