The woman's symptoms began at 18 months of age with involuntary movements of the shoulders and hands, intermittent head jerks, and toe walking. Over the following decades the disorder progressed slowly, with the emergence of cervical dystonia, generalized choreiform dyskinesias, gait impairment, truncal dystonia, and dysarthria. Crucially, several features classically associated with ataxia-telangiectasia never appeared: cerebellar ataxia, telangiectasia, immunodeficiency, and respiratory involvement remained absent throughout her life.

A similar movement disorder was present in her younger sister, pointing to a hereditary cause and suggesting autosomal recessive inheritance. Despite extensive neurological, metabolic, and genetic investigations over almost four decades, no molecular diagnosis had been reached. Brain magnetic resonance imaging was repeatedly normal, and targeted genetic testing for common hereditary dystonias came back negative, leaving the family in diagnostic limbo.

The diagnostic breakthrough came in stages. It was only when the exome data were reanalyzed several years later that a second pathogenic ATM variant, NM_000051.4:c.8147T>C, was detected, completing the biallelic picture and establishing the diagnosis of variant ataxia-telangiectasia. What makes this case striking is the phenotype itself.

By demonstrating that childhood-onset dystonic choreoathetosis can precede the classical manifestations of variant ataxia-telangiectasia by several decades, or occur in their absence, the report widens the range of presentations under which ATM-related disease may need to be considered. The authors frame the case within the broader challenge of combined dystonia, which they describe as a heterogeneous group of movement disorders with numerous genetic causes, making diagnostic evaluation difficult. In this family, the combination of a suggestive inheritance pattern, normal brain imaging, and negative targeted testing for common hereditary dystonias left the disorder unexplained for decades until exome sequencing, and ultimately its reanalysis, supplied the answer.

The years-long gap between the first sequencing run and the identification of the second ATM variant is central to the report's message. The authors highlight the diagnostic value of repeated reinterpretation of exome sequencing data in patients with unresolved hereditary movement disorders, and this family serves as a concrete demonstration that a single heterozygous pathogenic variant in a gene linked to a recessive disease may not be the end of the investigation. For affected families, a molecular diagnosis can end a diagnostic odyssey that in this case lasted nearly four decades.

The report is a single-family case study, and the authors note that all claims expressed in the article are solely those of the study team; the final, formatted version of the paper is forthcoming. Within those limits, the case documents a phenotype and a diagnostic pathway that had not previously been linked in this way. Variant ataxia-telangiectasia, as illustrated here, may manifest as a movement disorder dominated by dystonia and chorea while the features that usually define the condition remain absent.

For clinicians confronting familial dystonic choreoathetosis without a molecular explanation, the report suggests that biallelic ATM variants belong among the possible causes, and that returning to previously generated exome data may reveal answers that were present in the data all along.

Subject of Research: A familial case of dystonic choreoathetosis diagnosed as variant ataxia-telangiectasia caused by biallelic ATM variants

Article Title: Familial dystonic Choreoathetosis associated with Biallelic ATM variants

Article References: Godava, M., Satke, L., Otruba, P., Kanovsky, P., Rosales, R. L., Palata, V., & Šantavá, A. (2026). Familial Dystonic Choreoathetosis Associated with Biallelic ATM Variants. Frontiers in Neurology, 17, 1973543. https://doi.org/10.3389/fneur.2026.1973543

Image Credits: AI Generated

DOI: 10.3389/fneur.2026.1973543

Keywords: ATM gene, variant ataxia-telangiectasia, dystonic choreoathetosis, dystonia, exome sequencing, reanalysis, autosomal recessive inheritance, movement disorders, neurogenetics, diagnostic odyssey, familial, dystonic