Monozygotic twins with a new compound heterozygous SPG11 mutation and different disease expression

Abstract

Background: A pair of monozygotic 22-year-old twins with complicated hereditary spastic paraplegia caused by a novel SPG11 mutation is described.

Methods: Genetic testing and thorough clinical examination, magnetic resonance imaging (MRI) and MR-spectroscopy were performed.

Results: The twins were compound heterozygous for a known frameshift as well as a novel splice site mutation in the SPG11 gene. Clinically the patients showed a similar spectrum of symptoms but different disease presentation. MRI studies including morphometry and regional microstructural analysis by diffusion tensor imaging (DTI) of the corpus callosum (CC) by 3T MRI revealed marked thinning and corresponding increases of radial diffusivity (RD) and apparent diffusion coefficient (ADC) and reduction of the fractional anisotropy (FA) as compared to controls in all CC sections, particularly in the anterior callosal body. There was marked mainly supratentorial white matter reduction and to a lesser extent grey matter reduction in both patients. Involvement of the cortico-spinal tracts was reflected by FA and RD alterations. The more strongly affected patient showed a higher degree of callosal microstructural damage and cervical cord atrophy.

Conclusions: This study shows a similar symptom spectrum, but distinct clinical and imaging findings in monozygotic twins suffering from SPG 11, suggesting individual downstream genetic effects and/or non-genetic modifiers.

Keywords: Cognition; Corpus callosum; Diffusion tensor imaging; Hereditary spastic paraplegia; MRS; Magnetic resonance spectroscopy; SPG11; Spatacsin; Volumetry.