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54 - Spinal and bulbar muscular atrophy (Kennedy's disease): a sex-limited, polyglutamine repeat expansion disorder

from Part IX - Motor neuron diseases

Published online by Cambridge University Press:  04 August 2010

M. Flint Beal ,
Anthony E. Lang  and
Albert C. Ludolph
By
Patrick S. Thomas  and
Albert R. La Spada
M. Flint Beal
Affiliation:
Cornell University, New York
Anthony E. Lang
Affiliation:
University of Toronto
Albert C. Ludolph
Affiliation:
Universität Ulm, Germany
Patrick S. Thomas
Affiliation:
Department of Laboratory Medicine and Center for Neurogenetics and Neurotherapeutics, University of Washington Medical Center, Seattle, WA, USA
Albert R. La Spada
Affiliation:
Department of Laboratory Medicine, Medicine and Neurology and Center for Neurogenetics and Neurotherapeutics University of Washington Medical Center, Seattle, WA, USA
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Summary

Clinical background

In 1968, William Kennedy and co-workers described a slowly progressive neuromuscular disease in male members of two families (Kennedy et al., 1968). The “Kennedy's disease” syndrome that they reported was most consistent with a spinal muscular atrophy, but exhibited rather unique genetic and clinical features that differentiated it from other well-described motor neuron diseases at that time (Table 54.1). A number of other case reports describing patients with similar findings soon followed, establishing “Kennedy's disease” as a single specific genetic entity. Further work supported the classification of Kennedy's disease as a sex-linked form of spinal muscular atrophy that involved the bulbar musculature (Harding et al., 1982; Ringel et al., 1978; Stefanis et al., 1975). Because of the bulbar involvement, the disorder also came to be known as spinal and bulbar muscular atrophy, and “SBMA” was selected as its official genetic designation. While much has been learned about the pathogenesis and molecular basis of SBMA in the last 35 years, the original description provided by Dr. Kennedy and his colleagues remains an accurate clinical and laboratory vignette of what we now know as Kennedy's disease or SBMA.

SBMA is a slowly progressive motor neuronopathy that shows an X-linked pattern of inheritance, fully affecting only males. Dysfunction followed by gradual loss of motor neurons occurs in the anterior horn of the spinal cord and in the bulbar nuclei of the brainstem, while upper motor neurons are spared.

Type
Chapter
Information
Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
 , pp. 803 - 816
Publisher: Cambridge University Press
Print publication year: 2005

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