Clinical and electrophysiologic variability in amyotrophic lateral sclerosis within a kindred harboring the C9ORF72 repeat expansion

Abstract

Our objective was to characterize the motor neuron disease features within a large c9FTD/ALS kindred. We analyzed clinical, electrophysiologic and neuropathologic data in a c9FTD/ALS kindred of Scandinavian ancestry. Results showed that of six family members affected, three had only ALS, two had FTD and one had FTD and ALS. Each patient with motor neuron disease had a different clinical presentation: one patient had only bulbar symptoms, one had bulbar and limb involvement, one had limb symptoms, and one had primarily upper motor neuron disease. Later in the course of disease, all ALS patients developed bulbar involvement and died from respiratory causes. Survival was uniformly short (two to five years). Electrophysiologic studies recorded progressive lower motor neuron dysfunction except in the patient with predominantly upper motor neuron features. In conclusion, this kindred demonstrates that the presentation of ALS within c9FTD/ALS families may vary considerably and electrophysiologic findings reflect this heterogeneity.

Key words::

• Amyotrophic lateral sclerosis
• primary lateral sclerosis
• frontotemporal dementia

Acknowledgements

We appreciate the care provided to this family by the late Emre Kokmen and Edward H. Lambert. We particularly extend our appreciation to this family for participating in research on aging and neurodegenerative disease.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Rosa Rademakers and Mariely DeJesus- Hernandez have a patent pending on the discovery of the hexanucleotide repeat expansion in the C9orf72 gene. This study was funded by grants from the ALS Association, and Robert H. and Clarice Smith and Abigail van Buren Alzheimer's Disease Research Program of the Mayo Foundation.