Abstract
Kennedy's disease, also known as bulbospinal muscular atrophy (BSMA), is a rare, adult-onset,
X-linked, recessive trinucleotide, polyglutamine (poly-G) disorder, caused by expansion
of an unstable CAG-tandem-repeat in exon 1 of the androgen-receptor (AR) gene on chromosome
Xq11-12. Poly-Q-expanded AR accumulates in nuclei, undergoes fragmentation and initiates
degeneration and loss of motor neurons and dorsal root ganglia. Phenotypically, patients
present with weakness and wasting of the facial, bulbar and extremity muscles, sensory
disturbances, and endocrinological disturbances, such as gynecomastia and reduced
fertility. In the limb muscles weakness and wasting may be symmetric or asymmetric,
proximal or distal, or may predominate at the lower or upper limb muscles. There may
be mild to severe hyper-CK-emia, elevated testosterone or other sexual hormones, abnormal
motor and sensory nerve conduction studies, and neuropathic or rarely myopathic alterations
on muscle biopsy. BSMA is diagnosed if the number of CAG-repeats exceeds 40. No causal
therapy is available but symptomatic therapy may be beneficial for weakness, tremor,
endocrinological abnormalities, muscle cramps, respiratory failure, or dysphagia.
The course is slowly progressive and the ability to walk lost only late in life. Only
few patients require ventilatory support and life expectancy is only slightly compromised.
Abbreviations:
17-AAG (17-allyl-amino-17-demethoxy-geldanamycin), AR (Androgen-receptor), ASC-J9 (1,7-bis(3,4-dimethoxyphenyl)-5-hydroxy-1E,4E,6E-heptatriene-3-one), BSMA (Bulbospinal muscular atrophy), CBP (cAMP-response element binding protein), CAP-gly (Cytoskeleton-associated protein glycine-rich), CNS (Central nervous system), CSF (Cerebrospinal fluid), CHIP (Cognate hsp70-interacting protein), CMAPs (Compound muscle action potential), CK (Creatine-kinase), CAG (Cytosine–adenosin–guanosin), CREB (CRE-binding protein), DHT (Dihydro-testosterone), 17-DMAG (17-(dimethyl-aminethyl-amino)-17-demethoxy-geldanamycin), EB1 (Microtuble-binding protein), EMG (Electromyography), GGA (Geranyl–geranyl–acetone), HDJ (Co-chaperone of hsp70), HDAC (Histone-deacetylase), HSDJ (Human HSP40 homologue), HSNA (Hereditary sensory and autonomic neuropathy), Hsp (Heat shock protein), JNK (Jun-N-terminal kinase), MUNE (Motor unit number estimation), NEDD (Neuronal precursor cell-expressed developmentally downregulated protein), NLS (Nuclear localization signal), PGC-1 (Peroxisome proliferator-activated receptor gamma coactivator-1), Poly-G (Polyglutamine), Sir2 (Sirtuin 2), SNAP (Sensory nerve action potential), TGF (Tumor growth factor), UPS (Ubiquitine protease system), VEGF (Vascular endothelial growth factor)Keywords
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Article info
Publication history
Published online: September 16, 2010
Accepted:
August 23,
2010
Received in revised form:
August 15,
2010
Received:
June 19,
2010
Identification
Copyright
© 2010 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
