Many migraineurs have other family members who also suffer with migraine
headache. Mom used to have migraine headaches with her menstrual cycle,
grandmother once had "sick" headaches, and brother has "sinus" headaches
which are less severe but sound strangely similar to migraine if you ask
questions about symptoms and triggers.
For years scientists have argued whether disorders such as migraine that
tend to run in families do so because of shared genes or the shared environment.
People often assume that any disorder that occurs in several family members
must be genetic. However, families tend to share similar diets, exposures
and lifestyles, all of which might be involved in making someone susceptible
to a specific disorder. A combination of genetic and environmental factors
seems to be the best overall explanation for most common disorders, including
migraine.
Nevertheless, the fact that you occasionally find large families with many
members suffering from migraine suggest a stronger genetic basis for those
particular families. As it turns out, a definite inheritance pattern has
been found in a few families who suffer with a severe form of migraine called
hemiplegic migraine.
Hemiplegic Migraine: The inherited or "familial" form of hemiplegic
migraine is a rare disorder found in families where two or more people suffer
migraine-type headache associated with a "stroke-like" aura of weakness on
one side of the body. Other neurologic symptoms can also occur and might
include visual loss, difficulty with speech, confusion and numbness. In these
families, hemiplegic migraine has an autosomal dominant inheritance
pattern, meaning that if either the mother or father has the gene and passes
it on, that child will have hemiplegic migraine. So, on average, half of
the children in these hemiplegic families will suffer from the disorder.
In one half of the hemiplegic migraine families that we have identified,
the disorder is linked to a specific region on the 19th chromosone that includes
a calcium channel gene found in the brain.
The brain and nervous system depend on a combination of electrical and chemical
signals to do their work. A calcium channel is a type of a "gate"
on the end of a cell that is operated electrically. When an electrical impulse
of sufficient power (voltage) passes down a nerve cell, its calcium channel
opens and releases chemical messengers that contact the neighboring cells
and tell them how to respond. Serotonin and dopamine are a few of the many
chemical messengers found in the brain.
These families with hempilegic migraine have mutations that cause a certain
type of calcium channel to malfunction periodically. Some headache triggers
may preclude altered electrical impulses that lead to temporary calcium channel
malfunction, resulting in a series of biochemical changes that lead to a
migraine attack.
Regular Migraine: Thus far, we don't really know whether the defective
calcium channel gene found in these families with hemiplegic migraine genes
will prove to have a direct or indirect role in the pathways that produce
the much more common forms of migraine. The on-and-off, intermittent nature
of the defect in the calcium channel gene and its dependence on electrical
changes does make it a possible suspect for producing an episodic condition
such as migraine. There are other "voltage-gated" signaling systems in the
brain similar to the calcium channel, and these might also be involved in
regular migraine. We know that the migraine pathway ultimately involves
serotonin, dopamine and related chemicals in the brain, so many genes may
be involved.
It's more difficult to clearly identify genes associated with regular migraine,
given that environmental factors contribute significantly as well as genetic
factors. In general, common disorders are more likely to have many contributing
genetic influences, with different families showing distinct variations.
Distinguishing one gene from among several contributing genes and from background
environmental influences means that we need to study large numbers of patients
and many small families to achieve reliable and significant data.
The Next Step: There are still more questions than answers regarding
the genetics of migraine. Solving them will require imagination and the joint
effort of researchers from many different fields. We also need the continued
cooperation of migraine families and patients who have graciously participated
in genetic and clinical studies. Though we have our first genetic clue, we
now need to understand the consequences of the malfunctioning calcium channel.
We will be particularly interested in seeing if there are secondary effects
on serotonin and other brain chemicals that have been implicated in the
production of a migraine attack.
As other genes are identified, we can construct a better picture of the
biochemical pathways involved in migraine, beginning at the "starting point."
With this knowledge, we will have the opportunity to develop a wider range
of specific anti-migraine drugs that can block this pathway to stop the migraine.
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