Genetic Cause for Childhood Absence Epilepsy Identified
June 2, 2008 by Kristina Chew, PhD
Filed under Genetics, Health, Neuroscience
More genetics news today: Researchers have identified the mutated gene that causes childhood absence epilepsy (CAE).
The seizures of childhood absence epilepsy (CAE) are usually staring spells during which the child is not aware or responsive. The child’s eyes may roll up briefly. Each spell lasts about 10 seconds and ends abruptly. The child often is not even aware that anything has happened. These episodes can occur 1 to 50 times per day, often during exercise. Tonic-clonic (grand mal) seizures, with or without fever, may occur for a while before absence seizures develop and may occur from time to time thereafter. [Epilepsy.com]
The Childhood Absence Epilepsy Family Study also notes that CAE is also known as “Petit Mal” or epilepsy with “staring spells.” CAE is an inherited disorder and accounts for 10-12 percent of cases of childhood epilepsy.
The new study that points to a genetic cause for CAE appears in the May 29th online edition of the American Journal of Human Genetics. The study’s authors are from the David Geffen School of Medicine at UCLA and the Epilepsy Genetics/Genomics Laboratory, Epilepsy Center at the VA-Greater Los Angeles Healthcare System in West Los Angeles.
UCLA/VA research scientist Dr. Miyabi Tanaka studied the DNA of 48 patients with CAE and discovered that four patients had a genetic mutation occurring in a receptor called GABAR which binds to a neurotransmitter of the brain called GABA that inhibits the excitation of nerve cells in child and adult brains. When this regulation is lost or reduced, seizures develop.
“We identified this genetic mutation in eight percent of study patients with CAE, which is significant,” said Richard W. Olsen, Ph.D., study author and professor, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA.
Scientists also found that the genetic mutation was caused by an “alternative signal peptide called exon 1a, which is richly expressed in the fetus and developing brain, but as the child matures and becomes an adult, the expression of exon 1a is reduced”—-and this is why CAE “disappears” in adolescence and in adults.
We have wondered about the possibility of my son having seizures like the “absence seizures” noted above. Charlie’s pediatric neurologist specializes in epilepsy and seizures and (based on our descriptions of Charlie’s behavior) does not think he is having these types of seizures. Since my son’s language is very limited, we can never be 100% certain about anything, though—-hence the continuing interest in the possibility of medical signs and/or tests to detect conditions; to find answers.
Jeff Stimpson
Jill Cornfield
Always hungry for more information on this subject, so thank you. We are in the middle of deciding on a treatment course for my son’s absence episodes. Neurologists and other professionals had dismissed my concerns as “the typical spacing out of autism.” So I doubted myself until a few weeks ago, when he had a very clear episode in front of both me and his SLP.
Nice to hear that he might outgrow the episodes, but then again we don’t know if he’s in that mutant eight percent.
Ah, a subject with which we have intimate knowledge in our home. The best way to know for sure is to start keeping a log of when you see the “spells” (staring/space-out). Note the time fo day, the duration, the frequency AND the activity he was doing before, the behavior (if any) during, and how he is afterward. Keep a log for about a month so you can spot any trends/triggers, then ask the neuro to look at it and consider doing an ambulatory EEG.
In our case, we discovered that Nik WAS having seizures, especially at night, and he was put on meds. Two years later and he seems to have outgrown some of it and we are weaning one of his two meds with some pretty significant success —i.e., cognitive leaps, greater attention span, etc.
If you can touch Charlie’s nose or his eyelid during one of the “spells” and he doesn’t respond, it *could* be some seizure activity. Worth chceking out for sure! The toll untreated absence seizures can take can be significant over time.
I visited the page and winced when I saw Depakote described as the standard med. I know from bad experience that Depakote is one tough med to be on.
Kev is right. That’s the med we’re weaning right now. The neurological impact (and some of the potential physical side effects including elevated liver enzymes and longer-term liver damage) can be awful. Ironically, it was first given to Nik as an adjunct to his other med to help with what they thought might be migraines. In retrospect, we think it made things worse. As we’ve been weaning for a few weeks now, we see a decided improvement overall in Nik since decreasing the med. We’re hoping to lose it altogether!
Of course, Keppra was no walk in the park either; it made him very cranky and aggressive.
OUCH, not Depakote! Yeah, it’s broad spectrum but it’s HARSH. Just about anything that isn’t Tegretol or Trileptal is worth a shot, too…/nerd
I love Keppra but I’m kind of pharmacologically weird.
LOL at Kassiane’s comment re:”pharmacologically weird.” Seriously, I think I’ve read somewhere (waaay back when we tried the Keppra w/Nik) that the littler kids were the ones having many of the aggression/anger side effects from the Keppra. I have to wonder how much of that may also be a simple matter (well, maybe not quite “simple”) of communication ability, too. Nik at 2 1/2 was not able to communicate at all whereas Nik at 4 1/2 is really beginning to blossom. Tincture of time? Change in meds? Who knows?
This is something I wonder about. A pretty frequent thing for me is to “blank out” for a small time, such as in the middle of tae kwon do or in getting instructions. I wonder if it might be occurring a lot more frequent, but just that I don’t notice because most of the time in a day I’m not in the middle of listening to someone or doing exercise. I’ve been known to have the grand mal type seizures, but those were mostly during age 12 - 17, and very infrequent at that, which is why I never went on meds for it or anything.
Thank you for this information. My child has LKS, diagnosed after a marked regression in speech and gradual loss of age appropriate skills.
We have tried numerous epilepsy medications, which give our child a brief period of dramatic improvement, and then all the possible side effects of every med kick in.
Lamictal eventually caused day long migraines, topamax eventually caused hypoglycemic symptoms and agression, and caused my child to periodically lose consciousness for brief moments, depakote was a wonder drug for awhile till wild physical side effects kicked in, and we were told keppra causes agression and to not even try it.
Now my child is on trilpetal which has given us the longest periods of well-being and improvement, but after a week or two at most the migraine symptoms break through.
we cannot plan anything in advance and basically lead the life of caring for an invalid. my child is able to sporadically communicate in full complete complex sentences thoughts, feelings, and observations, which let us know that ‘its all still in there’ as a team of therapists told us. A very frustrating life for a child or adult.
I love Niksmom’s website and I thought the periodic episodes of pain might be a reaction to whatever epilepsy med he is taking, the symtoms were just too much like my own child to not be related.
After a 48 hour eeg on no meds we kept our child off meds for a week because he was so happy, verbal and easy going, like the child we remembered before his eeg readings got worse. But a week later, he was on the floor sobbing, holding his head in pain for a day and night, and we had to turn to trileptal. Instantly we saw an improvement, but then a week or two later the painful episodes come back. My child is just very sensitve to side effects of meds performing a powerful function and it is not a long term answer.
We do try to follow a diet low in carbs, food dyes, additives,sugar (including foods that quickly convert to sugar) during which we see a big improvement, but it is not enough. Special diets such as atkins for seizures and the ketogenic diet have long been successful for many children when meds fail…and since so many parents of children dx’d asd or pdd swear by special diets, I think there is a correlation.
Some children are found to have seizures even after a clear 24 hour eeg, so, I believe strongly that if a person appears in pain, it may be spikes or seizures and not ‘behavior’.
thanks, Caroline L. (also a huge fan of Niksmom’s site and of Nik). I wonder often how much of Charlie’s head-banging was from something internal (a massive headache) that then also had behavioral aspects—-he’d do something, or perhaps we would (talk too loud or in certain pitches of voice, perhaps) and then he’d bang and we’d react. Charlie as you know is on different meds and they do help him; it’s also very important that we give them to him at consistent times. Always good to hear from you!