HSP differences in identical twins

Posted - December 2017 in Research Highlights

More than genetic inheritance at play

 

Despite being identical twins with the identical HSP mutation, this study found significant differences in clinical and brain imaging measures that matched with a difference in severity between the twins. This suggests that downstream genetic effects and/or non-genetic modifiers may significantly influence the level of disease severity and the course of HSP progression.

 

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.

 

SOURCE: J Neurol Sci. 2017 Oct 15;381:265-268. doi: 10.1016/j.jns.2017.09.005. Epub 2017 Sep 5. PMID: 28991695 Copyright © 2017 Elsevier B.V. All rights reserved.

 

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

 

Schneider-Gold C1, Dekomien G2, Regensburger M3, Schneider R4, Trampe N5, Krogias C6, Lukas C7, Bellenberg B8.

 

1 Department of Neurology, St. Josef-Hospital, Ruhr-University, Gudrunstraße 56, D-44791 Bochum, Germany. Electronic address: [email protected]

2 Department of Human Genetics, Ruhr-University, Universitätsstraße 150, D-44801 Bochum, Germany. Electronic address: [email protected]

3 Division of Molecular Neurology, University of Erlangen, Schwabachanlage 6, D-91054 Erlangen, Germany. Electronic address: [email protected]

4 Department of Neurology, St. Josef-Hospital, Ruhr-University, Gudrunstraße 56, D-44791 Bochum, Germany. Electronic address: [email protected]

5 Department of Neurology, St. Josef-Hospital, Ruhr-University, Gudrunstraße 56, D-44791 Bochum, Germany. Electronic address: [email protected]

6 Department of Neurology, St. Josef-Hospital, Ruhr-University, Gudrunstraße 56, D-44791 Bochum, Germany. Electronic address: [email protected]

7 Department of Radiology and Nuclear Medicine, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstraße 56, D-44791 Bochum, Germany. Electronic address: [email protected]

8 Department of Radiology and Nuclear Medicine, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstraße 56, D-44791 Bochum, Germany. Electronic address: [email protected].

 

 

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