Spectrum of Inherited Childhood-Onset Dystonia: Case Series of 19 Families With Genotype and Phenotype Characterization Highlighting the Treatable Causes

Childhood-onset dystonia, a clinically and genetically diverse group of disorders, can be challenging to diagnose. Information on the genotype and phenotype spectrum in the Indian population is limited. This study reports the clinical and molecular findings of monogenic childhood-onset dystonia in 22 individuals from 19 Indian families. Complex dystonia was the most frequent type, followed by combined and isolated forms. A total of 23 variants across 17 genes were identified, including nine novel ones. These disorders include four autosomal dominant, one X-linked recessive, one mitochondrial, and the remaining 11 autosomal recessive conditions. Five potentially treatable disorders were identified, and treatment was initiated in three families, showing satisfactory responses, particularly in dopa-responsive dystonias. Our study contributes four additional genes—CYP27A1, NDUFAF3, FUCA1, and FIG4—to the list of genes associated with complex dystonia. Exome sequencing proved crucial in diagnosing the etiology of dystonia, identifying treatable forms, and aiding genetic counseling. This study emphasizes the significance of using NGS for early genetic diagnosis to enable timely targeted therapies, offer precise genetic counseling to families, and prevent recurrence in the family.