Background: Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous neurodegenerative disorder characterized by progressive spastic paraparesis of the lower limbs.
Objective: To identify the genotype and characterize the phenotype in a family with a novel form of complicated autosomal recessive hereditary spastic paraparesis (ARHSP).
Methods: Six subjects of a Turkish family were examined by clinical evaluation, detailed neuropsychological testing, neurophysiologic studies, MRI, diffusion tensor imaging (DTI), and mutation analysis of SPG7 gene.
Results: Three individuals were affected by a juvenile-onset form of complicated ARHSP due to the missense mutation c.2075G>C in exon 15 of the SPG7 gene in the homozygous state, substituting serine with threonine at codon 692. As additional clinical features, cerebellar syndrome, supranuclear palsy, and cognitive impairment, particularly disturbance of attention and executive functions, were found. MRI showed cerebellar atrophy and mild frontal cerebral atrophy. DTI revealed bilateral disturbance of white matter integrity in corticospinal tracts, frontal lobes, and the midbrain.
Conclusions: The new SPG7 gene mutation leads to a novel complicated autosomal recessive hereditary spastic paraparesis phenotype that widens the spectrum of different brain systems that are optionally affected in hereditary spastic paraplegia (HSP). In this novel phenotype, spastic paraparesis is related to cerebral damage of corticospinal tracts. Impairment of attention and executive functions is due to white matter loss in frontal lobes. Furthermore, supranuclear palsy is caused by white matter damage in the midbrain. This multisystem affection, which was detected by the use of diffusion tensor imaging, may reflect a mitochondrial dysfunction that contributes to the underlying pathogenesis of SPG7-HSP.