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Novel mutations in SPG11 cause hereditary spastic paraplegia associated with early‐onset levodopa‐responsive Parkinsonism
Author(s) -
Guidubaldi Arianna,
Piano Carla,
Santorelli Filippo M.,
Silvestri Gabriella,
Petracca Martina,
Tessa Alessandra,
Bentivoglio Anna Rita
Publication year - 2011
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.23552
Subject(s) - hereditary spastic paraplegia , corpus callosum , parkinsonism , medicine , paraplegia , compound heterozygosity , spastic , pathology , mutation , neuroscience , psychology , genetics , physical medicine and rehabilitation , psychiatry , biology , phenotype , disease , spinal cord , gene , cerebral palsy
Background: Autosomal recessive hereditary spastic paraplegia with thin corpus callosum is a neurodegenerative disorder characterized by spastic paraparesis, cognitive impairment, and peripheral neuropathy. The neuroradiologic hallmarks are thin corpus callosum and periventricular white matter changes. Mutations in the SPG11 gene have been identified to be a major cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum and recently also proven to be responsible for juvenile parkinsonism associated with spastic paraplegia. Methods: We describe one Italian autosomal recessive hereditary spastic paraplegia with thin corpus callosum patient who unusually presented at onset, 16 years, with parkinsonism‐like features, responsive to dopaminergic therapy. Then the clinical picture evolved and became more complex. A brain magnetic resonance imaging scan showed thin corpus callosum and hyperintense T 2 ‐weighted lesions in periventricular regions, and the 123 I‐ioflupane single‐photon emission coupled tomography was abnormal. Results: Genetic analysis detected two novel mutations, a c.3664insT variant in compound heterozygosity with a c.6331insG mutation, in SPG11 . Discussion: This case confirms the high genetic and clinical heterogeneity associated with SPG11 mutations. It also offers further evidence that parkinsonism may initiate autosomal recessive hereditary spastic paraplegia with thin corpus callosum and that parkinsonian symptoms can have variable dopaminergic response in these patients. © 2011 Movement Disorder Society