The Oldest Known Case of <scp>SCA6</scp> : Diagnostic Insights from a 101‐Year‐Old Woman with Progressive Ataxia

Genetic neurological diseases in the elderly can be challenging to recognize given medical comorbidities, polypharmacy, and heterogenous clinical presentations, and are likely underdiagnosed.1 We report the oldest known case of a person diagnosed with spinocerebellar ataxia type 6 (SCA6) at age 101. This 101-year-old woman presented with a 21-year history of gradual onset progressive imbalance and incoordination beginning at age 80. Initial symptoms included unsteadiness when turning, leading to a fall and right arm fracture within a year. At age 95 she required a walker for ambulation, and later developed mild dysarthria and dysphagia. She lived alone until age 100 years. Her symptoms were attributed to aging and past injuries, with no consideration of a neurological cause. Her evaluation was prompted by her 74-year-old son's diagnosis of SCA6, the first in the family (Fig. 1, Table S1, Video 1). Her son presented with mild dysarthria, appendicular dysmetria and gait disturbance. Subsequently, her asymptomatic granddaughter requested genetic testing, which also showed a repeat expansion in the CANA1A gene. Neurological exam demonstrated scanning, dysarthric speech, jerky ocular pursuit, hypermetric horizontal saccades, mild–moderate dysmetria and dysdiadochokinesia in all limbs. Gait was unsteady, requiring two-person assistance (Video 2). Her SARA score was 25.5. Genetic testing demonstrated a 21 CAG repeat expansion in CACNA1A, confirming SCA6. This autosomal dominant (AD) disorder is characterized by slowly progressive, pure cerebellar ataxia, onset reported between ages 16–72 years.2 While clinical anticipation with earlier onset or increased severity might occur, CAG repeat size generally remains stable during intergenerational transmission, as observed in this case.3 Other hereditary ataxias can manifest in late adulthood, such as SCA27B, SCA31, and cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS).4 This case emphasizes the complexity of diagnosing hereditary movement disorders among the oldest patients. Elderly patients are more likely to accumulate medical comorbidities and polypharmacy, which can confound or overlap with late-onset genetic movement disorders.1 In these complex scenarios, genetic diseases are rarely considered in elderly patients. Hereditary neurological conditions may manifest with milder or different phenotypes at late disease onset. Genetic testing's expanding accuracy and accessibility have advanced our knowledge regarding hereditary disorders.5 Hereditary ataxias reported to have late onset presentations have increased and should be considered in elderly patients with gait and coordination disturbances in the right clinical scenario, including oculomotor abnormalities, progressive symptoms, upper limb incoordination, slurred speech, symptoms unexplained by or disproportionate to past medical history.4 Diagnosing hereditary diseases in the elderly has multiple relevant implications. For family members, it can bring awareness about an inheritable disease, prompting consideration of genetic counseling. As new disease-modifying therapies emerge, diagnosis may allow for an early intervention in younger family members. Natural history studies may help improve our understanding of pathogenic mechanisms, and intrafamilial clinical differences can bring light to other factors influencing age of onset and phenotype. Comparing clinical presentations at different ages of onset may help broaden phenotypic spectrums. This case underscores the importance of considering hereditary ataxias in the differential diagnosis of elderly patients with unexplained cerebellar symptoms, since timely diagnosis can have meaningful clinical implications for both patient care and family risk assessment. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique. N.L.: 1A, 1B, 1C, 3A. K.L: 1A, 1B, 1C, 3B. Ethical Compliance Statement: The authors confirm that the approval of an institutional review board was not required for this work. Written informed consent was obtained from the patient, including video recording. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Funding Sources and Conflict of Interest: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. Financial Disclosures for the previous 12 months: NL: The author declares that there are no additional disclosures to report. KL's research is supported by NIH grant 1KL2TR001444. She has served as a consultant for Prime. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. TABLE S1. Clinical, genetic and imaging features for family members with a CAG repeat expansion in CACNA1A from three generations. AO, Age of onset; PMH, Past medical history. 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