Case Report: clinical manifestations and imaging features associated with PANK2 c.940C>T variant in PKAN with symmetric basal ganglia calcification

BackgroundPantothenate kinase-associated neurodegeneration (PKAN) is the most common subtype of neurodegeneration with brain iron accumulation and is classically associated with pallidal iron deposition and the “eye-of-the-tiger” sign on MRI. However, atypical clinicoradiological presentations may complicate recognition.Case PresentationWe report a 35-year-old woman with adolescent-onset, slowly progressive dystonia characterized by involuntary mouth opening, tongue protrusion, abnormal limb posturing, gait impairment, and cognitive decline. Neuroimaging showed pallidal signal abnormalities compatible with an eye-of-the-tiger-like pattern together with symmetric basal ganglia calcification. Genetic testing identified a homozygous PANK2 variant, NM_001386393.1:c.940C>T [p.(Leu314Phe)], with family segregation consistent with autosomal recessive inheritance. According to the clinical laboratory report, the variant was classified as likely pathogenic under the ACMG/AMP framework (PM2_supporting, PM3_strong, and PP3_moderate). Conservation assessment, computational prediction, and structural modeling supported a deleterious effect, although direct functional validation was not available. Additional findings included acanthocytosis, mild hyperhomocysteinemia, and electrophysiological evidence of peripheral nerve involvement.ConclusionThis case highlights an atypical but clinically informative PKAN presentation in which pallidal iron deposition coexisted with symmetric basal ganglia calcification. PKAN should remain in the differential diagnosis of slowly progressive dystonia even when neuroimaging is not fully classic. The possible links among CoA dysregulation, iron deposition, calcification, and associated peripheral findings should be regarded as hypothesis-generating.