Atypical Pantothenate Kinase-Associated Neurodegeneration: Intrafamilial Heterogeneity and Response to GPi Deep Brain Stimulation

Background/Purpose: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare, autosomal recessive neurodegenerative disorder caused by mutations in the PANK2 gene. It is characterized by progressive movement disorders—most commonly dystonia and choreoathetosis. Classic PKAN typically presents in the first decade with rapid progression, whereas atypical forms have a later onset and a slower disease course.

Methods: We report two siblings with compound heterozygous mutations in PANK2, presenting with atypical PKAN.

Results: The older sibling, a boy, developed tongue tremor and oromandibular dystonia at age 10. Within 2 years, he progressed to severe laryngeal dystonia and complete aphonia, with multiple episodes of aspiration pneumonia, along with gradually worsening generalized dystonia. He was treated with trihexyphenidyl, clonidine, diazepam, and baclofen. At age 16, he underwent bilateral Globus pallidus internus deep brain stimulation (GPi-DBS), showing a favorable response, including unexpected improvement in laryngeal and oromandibular dystonia, allowing him to regain speech and resume oral intake 3 months post-DBS. His younger sister presented with mild lower limb dystonia at age 11. Within 2 years, she developed generalized dystonia with cranial and axial involvement, myoclonus, opisthotonic posturing, retropulsion, and loss of ambulation. Despite aggressive antidystonic polypharmacotherapy, she progressed to status dystonicus at age 13. She underwent GPi-DBS, resulting in a marked reduction in hyperkinetic movements, regaining ambulation within 3 weeks. At 6 months post-DBS, she maintained a sustained response, though retropulsion and axial dystonia continue to impair gait.

Conclusion: GPi-DBS is a therapeutic consideration for refractory dystonia in PKAN, although outcomes may vary. These cases highlight a favorable response to GPi-DBS, including notable improvement in oromandibular and laryngeal dystonia, which is typically resistant to DBS.

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Artikel online veröffentlicht:
26. September 2025