Characterizing the Phenotypic and Imaging heterogeneity of SCA27B: Insights from a Retrospective Analysis
Clinical Genetics and Therapeutics
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Primary Categories:
- Clinical-Adult
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Secondary Categories:
- Clinical-Adult & Pediatric
Introduction:
The goal of this study is to provide a comprehensive characterization of spinocerebellar ataxia type 27B (SCA27B), a rare and recently described neurodegenerative disorder. This study aims to detail the clinical presentation, radiographic features, and progression patterns associated with SCA27B, which is caused by heterozygous intronic GAA repeat expansions in the FGF14 gene. Understanding the clinic-radiologic spectrum would contribute valuable insights into SCA27B, enhancing diagnostic accuracy and informing future therapeutic development.
Methods:
A retrospective analysis was conducted on clinical data including review of clinical charts, imaging and other diagnostic testing from 16 patients at our institution over a period of two years (2022 -2024) who were diagnosed with SCA27B based on genetic confirmation in the appropriate clinical context. Data extracted from medical records included demographics, family history, age of symptom onset, symptom profile, neurological examination findings, neuroimaging results, and treatment history.
Results:
A total of 16 patients were included. Age at symptom onset ranged from young adulthood to late adulthood (26 – 80 years). All patients had mono-allelic pathogenic expansion in FGF14. The cohort displayed a wide range of clinical symptoms, underscoring the phenotypic variability of SCA27B.
MRI Brain: There was mild cerebellar atrophy, most often affecting the vermis, seen in about 50% of the cases. This finding did not seem to correlate with severity or progression of the symptoms.
EMG was performed on nine of the sixteen patients (56%), revealing a spectrum of findings ranging from normal results to sensory and motor neuropathy, axonal sensorimotor polyneuropathy, radiculopathy, and carpal tunnel syndrome (18% EMGs were abnormal).
Vestibular evaluation was conducted in nine of the sixteen subjects (56%) and yielded normal results in all cases, suggesting a central origin for the imbalance and vertigo.
Conclusion:
This restrospective study of case series underscores the complex and variable clinical presentation of SCA27B, characterized by prominent cerebellar dysfunction and ocular symptoms. Clinicians should suspect SCA27B in middle aged to older patients presenting with imbalance, often trigged by movement, downbeat nystagmus and gait difficulties. MRI Brain showed mild cerebellar atrophy often involving vermis in about 50% of the patients, this however did not correlate with severity or duration of symptoms in our cohort. Periodic genetic reevaluation of patients with negative genetic workup in the past is essential as the intronic expansion of FGF14 was only recently described. Larger cohort studies looking at the natural history and progression of this disorder is imperative for a deeper understanding of the full spectrum of SCA27B manifestations and develop more effective strategies for diagnosis, management, and treatment.
The goal of this study is to provide a comprehensive characterization of spinocerebellar ataxia type 27B (SCA27B), a rare and recently described neurodegenerative disorder. This study aims to detail the clinical presentation, radiographic features, and progression patterns associated with SCA27B, which is caused by heterozygous intronic GAA repeat expansions in the FGF14 gene. Understanding the clinic-radiologic spectrum would contribute valuable insights into SCA27B, enhancing diagnostic accuracy and informing future therapeutic development.
Methods:
A retrospective analysis was conducted on clinical data including review of clinical charts, imaging and other diagnostic testing from 16 patients at our institution over a period of two years (2022 -2024) who were diagnosed with SCA27B based on genetic confirmation in the appropriate clinical context. Data extracted from medical records included demographics, family history, age of symptom onset, symptom profile, neurological examination findings, neuroimaging results, and treatment history.
Results:
A total of 16 patients were included. Age at symptom onset ranged from young adulthood to late adulthood (26 – 80 years). All patients had mono-allelic pathogenic expansion in FGF14. The cohort displayed a wide range of clinical symptoms, underscoring the phenotypic variability of SCA27B.
- Predominant Cerebellar Features: Gait and balance disturbances, including ataxia (25%), imbalance (87.5%), and frequent falls (37%), were prominent findings in the majority of patients. Oculomotor abnormalities, such as nystagmus (56%), oscillopsia (31%), and diplopia (43%), were also frequently observed.
- Varied Symptom Onset and Progression: While the overall data suggested a progressive course, the rate and pattern of symptom evolution varied considerably, with some patients experiencing slow, insidious progression and others exhibiting more rapid or episodic deterioration.
- Additional Neurological Manifestations: Dysarthria (slurred speech) and dysphagia (difficulty swallowing) were common findings, often worsening over time. Tremors, weakness, and sensory disturbances were also reported in a subset of patients. Ophthalmological examination often noted ( downbeat or gaze evoked) nystagmus, skew deviation, hypometric saccades and mild saccadic pursuits.
- Limited Insights into Cognitive and Autonomic Involvement: Cognitive changes and autonomic dysfunction were noted in small proportion of patients(25% and 12.55% respectively).
- Treatment Outcomes: Several medications were tried in this cohort, including dalfampridine, clonazepam, riluzole, 4-aminopyridine, amantadine, and acetazolamide. Some patients reported modest improvement with medications like dalfampridine or amantadine, while others experienced no benefit or side effects.
MRI Brain: There was mild cerebellar atrophy, most often affecting the vermis, seen in about 50% of the cases. This finding did not seem to correlate with severity or progression of the symptoms.
EMG was performed on nine of the sixteen patients (56%), revealing a spectrum of findings ranging from normal results to sensory and motor neuropathy, axonal sensorimotor polyneuropathy, radiculopathy, and carpal tunnel syndrome (18% EMGs were abnormal).
Vestibular evaluation was conducted in nine of the sixteen subjects (56%) and yielded normal results in all cases, suggesting a central origin for the imbalance and vertigo.
Conclusion:
This restrospective study of case series underscores the complex and variable clinical presentation of SCA27B, characterized by prominent cerebellar dysfunction and ocular symptoms. Clinicians should suspect SCA27B in middle aged to older patients presenting with imbalance, often trigged by movement, downbeat nystagmus and gait difficulties. MRI Brain showed mild cerebellar atrophy often involving vermis in about 50% of the patients, this however did not correlate with severity or duration of symptoms in our cohort. Periodic genetic reevaluation of patients with negative genetic workup in the past is essential as the intronic expansion of FGF14 was only recently described. Larger cohort studies looking at the natural history and progression of this disorder is imperative for a deeper understanding of the full spectrum of SCA27B manifestations and develop more effective strategies for diagnosis, management, and treatment.