What are the clinical features of Spinocerebellar Ataxia 25 (SCA25)?

Clinical Features of Spinocerebellar Ataxia 25 (SCA25)

Spinocerebellar Ataxia 25 (SCA25) is primarily characterized by progressive cerebellar ataxia with severe sensory neuropathy, which manifests during the course of the disease 1. This rare form of autosomal dominant cerebellar ataxia has distinctive clinical and imaging features that differentiate it from other SCAs.

Key Clinical Manifestations

• Cerebellar Ataxia:

  • Unsteady, irregular stepping pattern
  • Wide-based stance
  • Variable step length and timing
  • Lateral veering or swaying 2
  • Dysarthria and ocular dysmetria 3

• Sensory Neuropathy:

  • Severe axonal sensory neuropathy 4, 5
  • Proprioceptive deficits leading to sensory ataxia
  • Worsening with eyes closed (positive Romberg test) 3
  • High-stepping, stomping gait 2

• Disease Onset and Progression:

  • Variable age of onset, ranging from early childhood to adulthood 4
  • Progressive course with worsening cerebellar and sensory symptoms 4
  • Clinical variability ranges from incomplete penetrance to a Friedreich ataxia-like syndrome 1

Neuroimaging Findings

• MRI Brain:

  • Cerebellar atrophy 4
  • Cerebellar cortex hyperintensities 4
  • Dentate nuclei hyperintensities 4
  • MRI is the preferred imaging modality for evaluation 3, 2

• Electrophysiological Features:

  • Abnormal sensory nerve conduction studies showing axonal sensory neuropathy 4, 5
  • Mixed axonal and demyelinating characteristics may be present 5
  • Abnormal somatosensory evoked potentials (SEPs) 6

Genetic Basis

• Associated with pathogenic variants in the PNPT1 gene 4
• Autosomal dominant inheritance pattern 1
• Incomplete penetrance has been documented 4
• Originally mapped to chromosome 2p 1

Distinctive Features from Other SCAs

• SCA25 demonstrates more severe sensory neuropathy compared to SCA1, SCA2, and SCA3 5, 6
• Unlike SCA6, which has less peripheral nerve involvement (22% vs. 55-82% in other common SCAs) 5
• First reported cerebellar gray matter hyperintensities in SCA25, which can be a distinguishing imaging feature 4

Clinical Course and Management

• Progressive worsening of symptoms over time 4
• No specific disease-modifying treatments are currently available 7
• Management focuses on symptomatic treatment and rehabilitation:
  • Physical therapy for ataxia and balance
  • Occupational therapy for daily activities
  • Speech therapy for dysarthria
  • Adaptive equipment as needed 7
  • Medications that may improve symptoms: amantadine, buspirone, or acetazolamide for incoordination; clonazepam or propranolol for tremor 7

Important Considerations

• SCA25 should be included in the differential diagnosis of early-onset progressive cerebellar ataxias, particularly when associated with sensory neuropathy 4
• Genetic testing is essential for definitive diagnosis 2
• MRI brain without contrast is the gold standard imaging modality for evaluating cerebellar lesions 2
• Regular follow-up is necessary to monitor disease progression and manage complications 7