Objective: To describe a case of lifelong motor incoordination, mirror movements, and possible dystonia caused by a novel likely pathogenic variant in the DCC gene.

Background: Loss-of-function mutations in the DCC gene are associated with autosomal dominant congenital mirror movements (CMMs) and/or agenesis of the corpus callosum, with incomplete penetrance and variable expressivity. Mirror movements, characterized by involuntary movements on one side of the body mirroring intentional movements on the opposite side, can be seen in both Parkinsonian and dystonic disorders. They are a hallmark clinical feature of the CMM syndrome, where they typically persist throughout life without progression. Phenotypic variability among individuals with DCC variants ranges from isolated mirror movements to episodic dystonia, developmental delay, intellectual disability, and neuropsychiatric symptoms. Since the DCC gene was first linked to CMMs in 2010, its inclusion in commercial genetic testing panels has been inconsistent, contributing to diagnostic delays.

Method: A 45-year-old woman presented with lifelong motor incoordination, cramping, and upper limb dystonia with overflow and mirror movements. Family history revealed similar hand posturing in multiple maternal relatives, none of whom had undergone formal evaluation or genetic testing. In 2019, an 18-gene dystonia panel was ordered at another institution, which returned normal, and no further testing was recommended. Upon presentation to our clinic in 2024, more comprehensive genetic testing was obtained, and a ~900-gene movement disorder panel was pursued (WES/WGS was not ordered due to insurance coverage/cost). Testing identified a novel heterozygous DCC nonsense variant, DCC:c.1178C>G (p.Ser393*), predicted to result in premature protein termination.

Results: This case identifies a novel likely pathogenic DCC variant associated with CMM syndrome, not previously reported in literature or population databases.

Conclusion: This case highlights the importance of comprehensive genetic testing to avoid diagnostic delay, inform prognosis, guide management strategies, and support accurate familial risk assessment.

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Srour, M., Rivière, J. B., Pham, J. M., Dubé, M. P., Girard, S., Morin, S., Dion, P. A., Asselin, G., Rochefort, D., Hince, P., Diab, S., Sharafaddinzadeh, N., Chouinard, S., Théoret, H., Charron, F., & Rouleau, G. A. (2010). Mutations in DCC cause congenital mirror movements. Science (New York, N.Y.), 328(5978), 592. https://doi.org/10.1126/science.1186463

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MDS Abstracts - https://www.mdsabstracts.org/abstract/novel-dcc-variant-identified-to-cause-congenital-mirror-movements/