Familial dystonic Choreoathetosis associated with Biallelic ATM variants

Combined dystonia represents a heterogeneous group of movement disorders with numerous genetic causes, making the diagnostic evaluation challenging. We report a 46-year-old woman with childhood-onset familial dystonic choreoathetosis who remained without a molecular diagnosis for almost four decades despite extensive neurological, metabolic, and genetic investigations. A similar movement disorder was present in her younger sister, suggesting a hereditary aetiology and autosomal recessive inheritance. The proband’s first symptoms appeared at 18 months of age as involuntary movements of the shoulders and hands, intermittent head jerks, and toe walking. The disorder progressed slowly during childhood and adulthood, with the subsequent development of cervical dystonia, generalized choreiform dyskinesias, gait impairment, truncal dystonia, and dysarthria, while cerebellar ataxia, telangiectasia, immunodeficiency, and respiratory involvement remained absent. Brain magnetic resonance imaging was repeatedly normal, and targeted genetic testing for common hereditary dystonias was negative. Initial clinical exome sequencing identified only a single pathogenic Ataxia-Telangiectasia Mutated gene ( ATM ) variant. Reanalysis of the exome several years later detected a second pathogenic ATM variant (NM_000051.4:c.8147 T > C), establishing the diagnosis of variant ataxia-telangiectasia caused by biallelic ATM variants. This case expands the phenotypic spectrum of variant ataxia-telangiectasia by demonstrating that childhood-onset dystonic choreoathetosis may precede the classical manifestations of the disease by several decades or occur in their absence. Furthermore, it highlights the diagnostic value of repeated reinterpretation of exome sequencing data in patients with unresolved hereditary movement disorders.