X-linked disorder characterized by degeneration of
both sensory and lower motor neurons supplying the limb and bulbar
musculature caused by a defect in the androgen receptor. Extraocular muscles
are spared, possibly because of reduced numbers of androgen receptors in
Bulbospinal Neuronopathy; Kennedy Spinal and Bulbar
Muscular Atrophy; X-Linked Bulbospinal Muscular Atrophy.
Approximately 1:40-50,000 males are affected worldwide (seems
consistently more frequent in western Finland).
X-linked recessive (only males can express the
full phenotype). Affects mainly Caucasians and Asians, but not Africans. The genetic defect is located at
the DXYS1 marker on the proximal long arm of the X chromosome (Xq11-12).
Females are carriers.
Degeneration of sensory and motor neurons
supplying the limb and bulbar musculature, sparing extraocular muscles
(possibly because of reduced numbers of androgen receptors in these
muscles). Caused by an expanded trinucleotide (cytosine-adenine-guanine
[CAG]) repeat in the androgen receptor within the
first exon of the gene. The disease mechanism likely involves toxicity of an
expanded polyglutamine tract in the androgen receptor protein.
Electromyography and muscle histology demonstrate neurogenic atrophy.
Necropsy shows diffuse loss and atrophy of anterior horn cells in the spinal
Laboratory findings include elevated serum creatine
kinase, pronounced involutional changes in Leydig cells,
hypobetalipoproteinemia, and abnormalities in the androgen receptor gene.
This is a slowly progressing muscle atrophy associated with mild androgen insensitivity
that affects only males. Muscle atrophy is initially not obvious and usually starts between
20 and 50 years of age. Its onset is insidious and early signs may include difficulties
with walking and a tendency to fall. Deep tendon reflexes are decreased and some patients
complain about muscle cramps and/or intention tremor. The muscle weakness not only
involves the extremities, but also the facial muscles (including facial fasciculations).
Calf hypertrophy may occur. Over the following 10-20 years, most patients will start to
experience difficulties with climbing stairs or other strenuous efforts, while about one
third will even be wheelchair-bound. Most patients will also suffer from involvement of
bulbar muscles with dysphagia, dysarthria (with a change in the voice character, e.g., a
more nasal sound) and drooling. Bulbar palsy results in increased risk for aspiration and
consecutive pneumonias, which can rarely be life-threatening. Lower motor and primary
sensory neuropathy have been described and are due to degeneration of anterior horn cells
and dorsal root ganglia, respectively. The disease may be symmetrical or asymmetrical.
Gynecomastia is an almost constant finding and usually the first sign of
androgen insensitivity, manifesting already in adolescence. Testicular atrophy, erectile
dysfunction, oligospermia/azoospermia with decreased fertility or sterility, as well as
diminished secondary sex characteristics are frequently found. Diabetes mellitus has been
described in some patients. Life expectancy is usually not affected, except when
complications from aspiration/pneumonia arise.
Preoperative assessment should evaluate the degree of muscle weakness and assess the
neurologic function. Lung function tests may be indicated. Check fasting ...