Pantothenate Kinase-Associated Neurodegeneration (PKAN) is one type of NBIA (neurodegeneration with brain iron accumulation) disorder. Classic PKAN is characterized by an early age of onset and rapid progression. Common features include impaired gait, restricted visual fields, dystonia, dysarthria, rigidity, spasticity, hyperreflexia, extensor toe signs, pigmentary retinopathy, and possible cognitive impairment. Atypical PKAN is characterized by a late age of onset and slow progression. Common features include speech difficulties (palilalia, tachylalia, dysarthria, hypophonia), neurobehavioral changes (impulsivity, violent outbursts, depression, emotional lability), Parkinson-like symptoms, spasticity, hyperreflexia, extensor toe signs, and possible cognitive impairment. Most individuals with PANK2 mutations show brain iron accumulation on a T2-weighted MRI scan. This accumulation is specific to the globus pallidus and substantia nigra and appears as the “eye of the tiger” sign. PANK2 sequence analysis will detect mutations in over 98% of individuals with NBIA and the “eye of the tiger sign”, but in only 50% of individuals with a clinical diagnosis of NBIA.
Deletions and/or duplications in the PANK2 gene as causative of PKAN have been reported.