SPG11 Mutations Associated With a Complex Phenotype Resembling Dopa-Responsive Dystonia.

Area of Science:

• Genetics
• Neurology
• Rare Diseases

Background:

• Hereditary spastic paraplegia (HSP) typically manifests with spasticity, cognitive issues, and a thin corpus callosum.
• A complex case of HSP caused by SPG11 mutations presented initially with dopa-responsive dystonia (DRD), a presentation not previously documented.

Purpose of the Study:

• To describe a unique case of SPG11-related HSP presenting with dopa-responsive dystonia (DRD).
• To highlight the diagnostic utility of whole exome sequencing (WES) in identifying complex genetic neurological disorders.
• To expand the understanding of the genotype-phenotype spectrum of SPG11 mutations.

Main Methods:

• A case study of an 11-year-old boy with progressive generalized dystonia, bradykinesia, and gait disturbance.
• Diagnostic workup included brain MRI, 123I-ioflupane SPECT, and whole exome sequencing (WES).
• Levodopa treatment and globus pallidus internus (GPi) deep brain stimulation (DBS) surgery were evaluated.

Main Results:

• Whole exome sequencing identified transheterozygous variants in the SPG11 gene.
• The patient exhibited significant improvement in dystonia following GPi DBS surgery.
• Radiological findings included a thin anterior corpus callosum and presynaptic dopamine deficiency.

Conclusions:

• SPG11-related HSP should be considered in the differential diagnosis for patients presenting with DRD, parkinsonism, and spasticity.
• This case broadens the recognized clinical and genetic spectrum of HSP.
• GPi DBS may represent a viable therapeutic strategy for select HSP patients.