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Clinical heterogeneity of neurodegeneration with brain iron accumulation (Hallervorden‐Spatz syndrome) and pantothenate kinase‐associated neurodegeneration
Author(s) -
Thomas Madhavi,
Hayflick Susan J.,
Jankovic Joseph
Publication year - 2004
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.10650
Subject(s) - dystonia , parkinsonism , neurodegeneration , movement disorders , age of onset , choreoathetosis , psychology , neuroscience , medicine , pathology , disease
Hallervorden Spatz syndrome (HSS), also referred to as neurodegeneration with brain iron accumulation (NBIA), is a rare inherited neurodegenerative disorder with childhood, adolescent, or adult onset. Patients with HSS/NBIA have a combination of motor symptoms in the form of dystonia, parkinsonism, choreoathetosis, corticospinal tract involvement, optic atrophy, pigmentary retinopathy, and cognitive impairment. After the recent identification of mutations in the PANK2 gene on chromosome 20p12.3–p13 in some patients with the HSS/NBIA phenotype, the term pantothenate kinase‐associated neurodegeneration (PKAN) has been proposed for this group of disorders. To characterize clinically and genetically HSS/NBIA, we reviewed 34 affected individuals from 10 different families, who satisfied the inclusion criteria for NBIA. Relatives of patients who had clinical, magnetic resonance imaging (MRI), or pathological findings of NBIA were included in the study. Four patients were found to have mutations in the pantothenate kinase 2 ( PANK2 ) gene. We compared the clinical features and MRI findings of those with and without PANK2 mutations. The presence of mutation in the PANK2 gene is associated with younger age at onset and a higher frequency of dystonia, dysarthria, intellectual impairment, and gait disturbance. Parkinsonism is seen predominantly in adult‐onset patients whereas dystonia seems more frequent in the earlier‐onset cases. The phenotypic heterogeneity observed in our patients supports the notion of genetic heterogeneity in the HSS/NBIA syndrome. © 2003 Movement Disorder Society