External Laryngeal Tremor in Adult-Onset Alexander Disease: A Case Report

Area of Science:

• Neurogenetics
• Neurology

Background:

• Alexander disease is a rare genetic neurological disorder caused by mutations in the glial fibrillary acidic protein (GFAP) gene.
• Adult-onset Alexander disease (AOAxD) typically presents with a range of neurological symptoms, but external laryngeal tremor has not been previously reported.

Observation:

• A 43-year-old male presented with involuntary neck movements, characterized by rhythmic vertical movements of the laryngeal skeleton, soft palate, and tongue, along with lower limb dysmetria.
• Genetic analysis revealed a pathogenic GFAP variant (c.994G>A; p.(Glu332Lys)).
• Cerebrospinal MRI showed spinal cord and medulla oblongata atrophy, with hyperintensities in the cerebellum and cerebral white matter, consistent with AOAxD, including the characteristic 'tadpole sign'.

Findings:

• The case presented with external laryngeal tremor, palatopharyngeal tremor, and cerebellar ataxia, constituting a mild phenotype.
• This specific GFAP mutation has been reported in isolation only twice previously.
• The observed symptoms and imaging findings align with the diagnosis of AOAxD, underscoring the phenotypic variability of the disease.

Implications:

• This case expands the known clinical spectrum of adult-onset Alexander disease by documenting external laryngeal tremor.
• The findings suggest that GFAP gene mutations can manifest with a broader range of movement disorders than previously recognized.
• Further research is needed to fully characterize the infrequent presentations and genetic underpinnings of Alexander disease.