Objective: To describe a patient with a childhood-onset combined dystonia who was found to be a carrier of a novel mutation in the ATL1 gene.

Background: Combined dystonia is defined as a dystonia which appears along with other movement disorders such as myoclonus, chorea or parkinsonism. Dystonic postures may or may not be the predominant movement abnormalities. Variants in the ATL1 gene are associated with pure hereditary spastic paraplegia (HSP-ATL1), also known as SPG3A, with an autosomal dominant inheritance. HSP-ATL1 patients mostly present as early onset pure HSP, with rare cases presenting motor-sensory axonal neuropathy.

Method: A 43-year-old male presented with generalized choreiform movements in limbs and trunk, as well as craniocervical dystonia and proximal myoclonus. Strength and deep tendon reflexes were normal, and no pyramidal signs were observed. His father, brother and two paternal uncles had suffered from similar movements since childhood. Brain magnetic resonance showed marked symmetric atrophy of the basal ganglia, with involvement of the caudate, putaminal and globus pallidum nuclei. Cerebrospinal fluid, hematological, biochemical, autoimmunity and vitamin tests were unremarkable. A comprehensive electrophysiological study was normal.

Results: The patient was diagnosed with early onset persistent generalized combined dystonia with autosomal dominant inheritance. He was started on tetrabenazine with partial improvement but parkinsonism features arose. By genetic testing, the novel Y90H variant in the ATL1 gene was identified. Y90H is located within the a-helix-1 flanking a conserved GTPase motif, evolutionally highly conserved (PhyloP=8.04) and predicted to cause major functional disruption of atlastin (Polyphen=1.00). The other affected family members are not available for clinical evaluation or genetic testing so far.

Conclusion: Here we present a patient with a hereditary combined dystonia carrying a novel mutation in the ATL1 gene. Whether variants in this gene can cause some forms of combined dystonia should be further explored.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/combined-dystonia-in-a-patient-carrying-a-novel-atl1-gene-variant/