Studies Shed Light on Multiple Miscarriages of Boys,
& Girls With Duchenne Muscular Dystrophy
Girls with the Duchenne form of muscular dystrophy (DMD)
and boys who perish during fetal life can sometimes be conceived by the
same parents. Now, geneticist Eric Hoffman, a longtime research grantee
of the Muscular Dystrophy Association, says the two problems can be
related and aren't just coincidental.
Studies being conducted by
Hoffman, who is at the Center for Genetic Medicine at Children's
Hospital National Medical Center in Washington, with colleagues at Magee
Women's Hospital in Pittsburgh, have revealed part of the solution to
this rare but troubling genetic puzzle.
The clue lies among parents who
pass on to their children an unfortunate combination of two genetic
problems at the same time, Hoffman says. One is a mutation in the gene
for DMD on an X chromosome, and the other is a second genetic mutation,
one of a class of "X-linked lethal" genetic mutations, on another X
The "X-linked lethal" mutation,
when inherited by a boy, causes him to die as a fetus and the mother to
miscarry. In fact, Hoffman notes, it's the first major genetic cause
that's been found to underlie "unexplained multiple miscarriages" in the
population in general, probably accounting for some 15 percent of cases
of unexplained multiple miscarriages. These findings are published in
the September 2001 issue of the American Journal of Obstetrics and
Here's what happens:
Boys, who normally have only one X chromosome, die before birth if they inherit the lethal defect.
Girls, who normally have two X
chromosomes, don't die from inheriting the defect. In fact, they may not
even know they have it as long as their second X chromosome is free of
disease-causing genetic flaws.
However, if they also inherit a
nonlethal, X-linked disorder, such as Duchenne muscular dystrophy,
they'll develop that disorder. Usually, a girl would only become a
"carrier" of an X-linked disorder and not show the disease herself. She
would normally be protected by her second X.
The X-linked lethal defect
causes female fetuses to rely solely on their other X chromosome — even
if it's one that carries a disease-causing mutation, such as the one for
There are other circumstances
in which the protection of a "backup" X chromosome is wholly or
partially lost, leading to symptoms of DMD in girls. For more on this
subject, see www.mda.org/publications/Quest/q56girlsdmd.html.