Objective: To describe a unique case of co-occurring SMA2 and HD in a patient.

Background: Huntington’s Disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG trinucleotide repeat expansions in the HTT gene, leading to progressive motor dysfunction, psychiatric disturbances, and cognitive decline.[1] Antisense Oligonucleotide (ASO) therapy is being investigated to reduce mutant huntingtin (mHTT) protein expression. [2]. Spinal Muscular Atrophy (SMA) is a genetic motor neuron disease caused by biallelic SMN1 mutations, leading to insufficient survival motor neuron (SMN) protein. SMA2 presents in infancy or early childhood with significant motor impairment but spares respiratory function.[3] Nusinersen, an ASO therapy, enhances SMN2 splicing to increase SMN protein levels, improving motor function and survival. [4]–[6]. A 36-year-old female with genetically confirmed SMA2, on Nusinersen since age 19, was evaluated after her mother’s HD diagnosis (40 repeats). Genetic testing confirmed our patient also carried 40 CAG repeats in HTT. A retrospective review of medical records was done to evaluate her clinical course and response to therapy.

Method: Case report

Results: Our patient was diagnosed with SMA2 at 15 months by EMG and muscle biopsy. She had progressive limb weakness leading to wheelchair dependence and requiring full-time caregiver support. Since 2017, she has experienced progressive dysphagia and dysphonia. She started intrathecal Nusinersen in 2018 which led to improvement in motor stamina and swallowing function. Genetic testing in 2024 confirmed HD, although both patient and her mother had no classical symptoms of hyperkinetic movements or neuropsychiatric disturbances beyond baseline anxiety and depression. Given the overlap of SMA-related dysphagia with potential HD-associated bulbar dysfunction, ongoing monitoring is warranted. While Nusinersen is not expected to influence HD pathology, this case provides an opportunity to observe HD progression in a patient on long-term ASO therapy, offering insights into neurogenetic overlap and disease-modifying strategies.

Conclusion: On our review of existing literature, there are no reports of co-occurrence of these two neurogenetic conditions. We seek to highlight the complexities of clinical prognostication in such cases. The interplay between SMA-related dysphagia and potential HD-associated swallowing dysfunction also warrants careful longitudinal evaluation.

References: [1] F. O. Walker, “Huntington’s disease.,” Lancet (London, England), vol. 369, no. 9557, pp. 218–228, Jan. 2007, doi: 10.1016/S0140-6736(07)60111-1.
[2] S. J. Tabrizi et al., “Potential disease-modifying therapies for Huntington’s disease: lessons learned and future opportunities.,” Lancet. Neurol., vol. 21, no. 7, pp. 645–658, Jul. 2022, doi: 10.1016/S1474-4422(22)00121-1.
[3] M. Oskoui and L. Servais, “Spinal Muscular Atrophy.,” Continuum (Minneap. Minn)., vol. 29, no. 5, pp. 1564–1584, Oct. 2023, doi: 10.1212/CON.0000000000001338.
[4] D. C. De Vivo et al., “Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: Interim efficacy and safety results from the Phase 2 NURTURE study.,” Neuromuscul. Disord., vol. 29, no. 11, pp. 842–856, Nov. 2019, doi: 10.1016/j.nmd.2019.09.007.
[5] E. Mercuri et al., “Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy.,” N. Engl. J. Med., vol. 378, no. 7, pp. 625–635, Feb. 2018, doi: 10.1056/NEJMoa1710504.
[6] R. S. Finkel et al., “Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy.,” N. Engl. J. Med., vol. 377, no. 18, pp. 1723–1732, Nov. 2017, doi: 10.1056/NEJMoa1702752.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/co-occurrence-of-spinal-muscular-atrophy-type-2-and-huntingtons-disease/