Intrafamilial Phenotypic Variability in the C9orf72 Gene Expansion: 2 Case Studies.

David Foxe,John R Hodges,Emma Devenney,Glenda M Halliday,Felicity V C Leslie,Elle Elan,James R Burrell,Olivier Piguet,John B Kwok

doi:10.3389/fpsyg.2018.01615

Abstract

The C9orf72 genetic mutation is the most common cause of familial frontotemporal dementia (FTD) and motor neuron disease (MND). Previous family studies suggest that while some common clinical features may distinguish gene carriers from sporadic patients, the clinical features, age of onset and disease progression vary considerably in affected patients. Whilst disease presentations may vary across families, age at disease onset appears to be relatively uniform within each family. Here, we report two individuals with a C9orf72 repeat expansion from two generations of the same family with markedly different age at disease onset, clinical presentation and disease progression: one who developed motor neuron and behavioural symptoms in their mid 40s and died 3 years later with confirmed TDP-43 pathology and MND; and a second who developed cognitive and mild behavioural symptoms in their mid 70s and 8 years later remains alive with only slow deterioration. This report highlights the phenotypic variability, including age of onset, within a family with the C9orf72 repeat expansion.

Highlights

Dementias are progressive neurodegenerative brain disorders caused by the abnormal accumulation of one or several proteins, neuronal death and brain atrophy over the course of many years
It is reported that Frontotemporal dementia (FTD) due to C9orf72 repeat expansions may have slower disease progression, more diffuse brain atrophy that tends to affect the parietal regions bilaterally, and a higher frequency of psychiatric features compared to sporadic cases (Galimberti et al, 2013; Devenney et al, 2014; Ducharme et al, 2017)
We described two individuals from the same family who both harboured an abnormal expansion of the C9orf72 gene

Summary

Introduction

Dementias are progressive neurodegenerative brain disorders caused by the abnormal accumulation of one or several proteins, neuronal death and brain atrophy over the course of many years. It is reported that FTD due to C9orf72 repeat expansions may have slower disease progression, more diffuse brain atrophy that tends to affect the parietal regions bilaterally, and a higher frequency of psychiatric features compared to sporadic cases (Galimberti et al, 2013; Devenney et al, 2014; Ducharme et al, 2017).

Results

Conclusion