It is very common to hear that women can't get SBMA due to the disease being X-linked. I think it is more correct to say that SBMA among women is extremely rare, but not impossible. Here's why.

In the U.S., about one in 40,000 men has the X-chromosome with the SBMA gene (the rate may be higher in some other nations such as Japan). So, assuming the gene is distributed evenly throughout the population, what is the probability of a woman having TWO X-chromosomes with this gene? Answer: one in 40,000 times 40,000, that is, one in 1.6 million.

That sounds like a very small number, but consider that the U.S. population is about 300 million people. Assume that about 150 million are women (which isn't perfectly accurate, but close enough for a rough estimate). The result is 150 million divided by 1.6 million, that is, approximately 94 women in the entire U.S. have the SBMA gene on both X-chromosomes.

Keep in mind that all women have some testosterone in their systems (just as all men have a little estrogen), and furthermore the changes in hormones that occur after menopause.

I think the obvious conclusion is that women CAN have SBMA, although it is exceedingly rare.

Dan, interesting math and hypothesis. We do know that women with one defective "X" can have minor symptoms and onset later in life. I can personally attest to that observing my mother. Leg weakness, hand tremors, and difficulty swallowing have been reported by several carriers in their later years.

Yes, the opportunity for two "X"s is rare, but not unheard of. Because KD is mainly associated with males, the treating physicians would probably have to have some family history of KD to even consider testing the woman for KD.

I found another source that may help this discussion. The Muscular Dystrophy Association (MDA) publishes a series of pamphlets which are distributed through doctors' offices. This material is written carefully and reviewed by medical authorities.

In publication P-181, under the heading "Can Women Develop SBMA?", here's what it says:

"Because SBMA is an X-linked disease, it usually affects men. However, in some cases, women can have the disease, although it's almost always a very mild case."

"The second X chromosome that females have is usually enough to protect them from most aspects of the disease. However, females (who also produce and use androgens, although less so than males) carrying the androgen receptor gene defect on one X chromosome can have muscle cramps and twitches, particularly as they get into their 60s or 70s. The hormonal differences between men and women may also contribute to the less severe course in women."

Here's an answer that has been published in a peer-reviewed medical journal. Following are two links to the article:
Neurology 59:770
and
NIH 12221177

This article, written by three doctors, reports on SBMA symptoms that were found in two sisters, age 34 and 42. Taken together with the other information in this thread, the answer is quite clear. Women do get symptoms of SBMA, but less severely than men.

The complete citation is:
Neurology. 2002 Sep 10;59(5):770-2.
Expression of X-linked bulbospinal muscular atrophy (Kennedy disease) in two homozygous women.
Schmidt BJ, Greenberg CR, Allingham-Hawkins DJ, Spriggs EL.

I found a reference to another reason why women can have SBMA symptoms. As you may know, women have two X-chromosomes. There is a natural process by which one X-chromosome can be "turned off" or inactivated. The process is called "X-inactivation" or "lyonization."

So, assuming the woman carrier had two X-chromosomes, one with the SBMA gene and second one without, and then the second X-chromosome became inactivated, then the first one with the SBMA gene would be more likely to be expressed.

Here's a quotation from Wikipedia:
"X-inactivation (also called lyonization) is a process by which one of the two copies of the X chromosome present in female mammals is inactivated....The choice of which X chromosome will be inactivated is random in placental mammals such as mice and humans, but once an X chromosome is inactivated it will remain inactive throughout the lifetime of the cell and its descendants in the organism."

This link points to the Wikipedia article on X-inactivation, for those who are interested.

Dan, that is really interesting. Thanks for sharing.

I am not sure if the X inactivation is the cause of the appearance of symptoms in females. There have been several cases in which both X chromosomes in women are the SBMA form of the gene (this is known as homozygous for SBMA) and these individuals do not show the symptoms as men do and are not really different from women who are simply carriers ( these are heterozygous). This paper was referenced in the post by Dan on this thread, I think the main reason women tend to have few symptoms is due to the low levels of testosterone. Since women do have testosterone, albeit low levels, it is possible that even these low levels of testosterone can lead to some of the minor (compared to men) symptoms. Still, I do not know of any report in which a woman has had the severity of symptoms seen in men.