How I Go On Living

Yesterday I was remembering an important moment with Daniel. In 2008, in the autumn, we were called to tell us that my father was in a hospital ICU in another city. He was very ill and was failing. I stayed with him for about four days, but on one Saturday, I thought it would do my father good to see his grandchildren, so my husband and oldest son, drove everyone up from Virginia. It was a trip which took hours. During those hours of travel, my Dad who would have enjoyed the visit, deteriorated significantly. When the kids arrived, I knew he knew they were there, but he could not wake and speak with them, and being nurses kids, they all noticed and knew a great deal about the apparent deteriorating heart rhythm on Dad'scardiac monitor. It was Daniel,especially,who was upset. Outside Dad's glass hospital room in the ICU, Daniel stood, with tears pouring down his face. I went over to him and hugged him tightly. I knew somehow that I wanted to hold that moment both frozen in time, and in my heart forever. When we let go, I told Daniel, that it was alright. (My) Dad's body was wearing out and he could no longer stay with us here on Earth and it was soon time for him to go to Jesus, where he would be comfortable, safe, and start on a new set of tasks. Somehow I was able to comfort Daniel, with my absolute and total belief in the hereafter. Of course, just 31 days after Dad's passing, Daniel too was called by God, in a manner which remains unclear, even after autopsy and multiple autopsy reviews by other experts, with continuing studies looking for genetic illnesses in blood and DNA. I hope.....no I pray, that the courage I showed to Daniel that day at the hospital out of state, was courage that helped him when only a short time later, God called him home. Sometimes, I am not quite sure how I go on living

Puzzles in Arrhythmia

Flowers beside the barn on the farm


The following article is interesting for those of us who lost a healthy child suddenly. However, Daniel's DNA was checked for these markers, and he did not have them. Our other children do not have lengthened QT intervals any time they have been checked, although one had a potassium dependent atrial fibrillation, as my father had.

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This article was found in:

Science Blog

http://scienceblog.com/932/mutation-causes-specific-arrhythmia-and-sudden-cardiac-death/

Mutation Causes Specific Arrhythmia and Sudden Cardiac Death

on February 5, 2003

An international team of researchers has demonstrated a genetic basis for a fatal form of inherited cardiac arrhythmia that usually strikes young, seemingly healthy people. Basing their research on a French family with a form (Type 4) of inherited Long QT Syndrome (LQTS) and experiments in mice, the researchers found the mutation in a specific gene encoding ankyrin-B, a protein within heart muscle cells. Their discovery identifies what appears to be a novel mechanism for cardiac arrhythmia.

From the Duke University Medical Center :
Mutation Causes Specific Arrhythmia and Sudden Cardiac Death

DURHAM, N.C. — An international team led by researchers from Duke University Medical Center and the Howard Hughes Medical Institute (HHMI) have demonstrated a genetic basis for a fatal form of inherited cardiac arrhythmia that usually strikes young, seemingly healthy people.

The results of the study were published in the Feb. 6, 2003 issue of the journal Nature.

Basing their research on a French family with a form (Type 4) of inherited Long QT Syndrome (LQTS) and experiments in mice, the researchers found the mutation in a specific gene encoding ankyrin-B, a protein within heart muscle cells. Their discovery identifies what appears to be a novel mechanism for cardiac arrhythmia.

Normally, ankyrin-B acts as a biochemical symphony conductor, ensuring that microscopic pores in heart muscle cells known as ion channels open and close in a coordinated fashion. These channels allow such chemicals as calcium, potassium, sodium and chloride to pass in and out of the cell with each heartbeat, thereby regulating the electrical activity of the heart.

“We have found a brand new mechanism for cardiac arrhythmias based on the coordination of these different ion channels,” said HHMI investigator and Duke cell biologist Vann Bennett, M.D., senior member of the research team. “It appears now that the arrhythmia arises, not due to some malfunction of the ion channels themselves, but a failure to ensure that multiple ion channels open at the right place and at the right time. Scientists have been looking for ion channel mutations, but they have not been able to find them.”

The QT interval is a measurement taken by electrocardiogram that represents the period of time from electrical stimulation of the heart’s pumping chambers to their recharging for the next heartbeat. In normal people, this interval ranges from 0.38 to 0.44 seconds. However, for people with LQTS, this period of recharging can be delayed up to 0.5 seconds, which put these patients at high risk for arrhythmias.

This constant back-and-forth electrical stimulation and recharging is controlled by different ions passing in and out of the cell, which alternately changes the cell’s polarization. About one-third of patients with the disorder never experience symptoms, but those who do can experience loss of consciousness, abnormal heartbeats or sudden death.

LQTS is a dominant genetic disorder, meaning that each child of a parent with the disorder has a 50-50 chance of getting the disease.

In 1995, the researchers identified a large family in France with a preponderance of members with LQTS. A specific mutation, known as E1425G, was found to be associated with LQTS in 22 of 24 of the family members and with abnormal heart rhythms in 23 out of 24 members. The mutation was not present in more than 400 control samples.

The researchers then examined effects of this mutation on the important ion channels that regulate calcium levels in heart cells using their ankyrin-B mutant mouse model of LQTS.

“We found that two normal copies of the ankyrin-B gene are necessary for normal calcium signaling, and that the E1425G mutation leads to a loss of function,” said Peter Mohler, Ph.D., HHMI post-doctoral fellow at Duke and first author of the paper. “So, ankyrin-B is the first identified protein implicated in a congenital LQTS that is not an ion channel.”

The team performed further comparisons between humans with LQTS and mice with the E1425G mutation of ankyrin-B, and found striking similarities in cardiac performance, including reduced heart rate, a high degree of heart rate variability and other heart rate disturbances that could not be linked to electrolyte or structural defects of the hearts. They also found similar loss of function in ion channels other than calcium.

“Sudden death in humans with this mutation usually occurred after physical exertion or extreme emotional stress,” Mohler said. “One of the members of the French family died suddenly at the age of 37 while running up a hill. So we wanted to see if this same effect would be present in the mouse models.”

To simulate these circumstances, the researchers exercised the mice and then injected them with epinephrine, one of the so-called “fight-or-flight” hormones that stimulate the heart.

“Of the 14 mice with the mutation, two became unresponsive seconds after exercise, and eight died following exercise combined with the injection,” Mohler said. “The effect was dramatic. None of the mice without the mutation showed any adverse effects from the exercise or the epinephrine.”

Bennett believes that the insights gained in these experiments could also have important implications for disorders of other organs, especially those that like the heart, have excitable membranes responsible for proper organ function. These organs include the nervous system, the lining of the lungs and the kidneys, and beta cells in the pancreas that are responsible for release of insulin.

The research was supported by the National Institutes of Health, the Muscular Dystrophy Association, the Canadian Institutes of Health, the Institut National de la Sante et de la Recherche Medicale, and the Programme Hospitalier de Recherche Clinique.

Other members of the team are: Jean-Jacques Schott, Karine Haurogne, Florence Kyndt and Denis Escander, Laboratoire de Physiopathologie et de Pharmacologie Cellulaires et Moleculaires, Hotel-Dieu, France; Herve Le Marec, Hospital G&R Laennec, Nantes, France; Keith Dilly, Silvia Guatimosim, William H. duBell, Long-Sheng Song, Terry Rogers and W.J. Lederer, University of Maryland; and from Duke, Anthony Gramolini and Mervat Ali.

How Puberty Hormones Can Trip Sudden Death Especially in Boys

Daniel at five


Daniel never fainted. He never gave us cause to wonder if anything was wrong. It is my hope that by informing others of this series of syndromes, that other sons and daughters may have these syndromes identified and treated,and can spent the rest of your life on Earth with you. Daniel also does not have any of the KNOWN genetic markers for LQTS, (Long QT Syndrome) or other conduction disorders, as identified by Mayo Clinic in lengthy genetic testing, completed on his blood retained from autopsy, only recently.


This is an interesting article from Science Daily.

ScienceDaily (Sep. 18, 2006) — Fainting during childhood, and whether a teen is going through the male or female changes of puberty, are among the factors that predict whether a genetic defect will suddenly stop the teen's heartbeat, according to a study published today in the Journal of the American Medical Association (JAMA). The study also found that treating teens at the highest risk for fatal arrhythmias with widely used blood pressure drugs reduced their risk by 64 percent.


Cardiac arrhythmias are electrical malfunctions that throw the heart out of rhythm, causing many of the 330,000 sudden cardiac deaths each year in the United States. Most fatal arrhythmias occur in aging patients when scar tissue left by a heart attack interferes with the heart's electrical system. As many as 1,000 of the deaths, however, are caused by a genetic disorder called Long QT Syndrome (LQTS), which occurs mostly in teens with otherwise healthy hearts.

The QT interval is part of the heart's electrical signature as recorded by an electrocardiogram (ECG). It represents the time it takes for the heart's lower chambers to "reset" electrically after each heartbeat. In LQTS patients, the QT reset time is prolonged, which makes the heart more susceptible to fatal arrhythmias. The condition may go unnoticed until sports, strong emotions or even loud noises knock the heart out of rhythm, causing loss of pulse and consciousness (syncope). Sudden death often results if the heart is not restarted with a defibrillator.

"LQTS shocks communities across the nation each year as teens die during sporting events," said Arthur Moss, M.D., professor of Medicine in the Department of Medicine at the University of Rochester Medical Center and an author of the JAMA paper. "It runs in families and can remain undiagnosed until the victim's brother or sister dies as well. New research has made clear the factors that accurately predict which kids are at high risk, factors that can be easily be monitored during routine office visits. We have the power to save more children through vigilance."

In 1979, Moss helped to launch the International Long QT Syndrome (LQTS) Registry, a database of families with the LQTS trait. By following generations of sufferers, gene hunters used the registry to track down more than 300 genetic mutations involving seven genes that cause versions of LQTS. By following the outcomes of patients in the registry over many years, researchers are now drawing accurate conclusions about risk.

Study Details

In current study, researchers went back and looked at 2,772 subjects from the LQTS Registry who were alive at age 10 and who were monitored by a physician until age 20. This is the largest LQTS study to date, and it is study the first to look at which risk factors are associated only with life-threatening events in teens, both those that ended in sudden cardiac death, and those where cardiac arrest was stopped by emergency treatment. Researchers found three significant predictors of life-threatening events in these patients: timing of prior fainting spells (syncope), the degree to which the QT interval was prolonged as measured by an ECG, and the patient's sex.

Statistical analysis revealed that children with two or more fainting spells in the two years prior to the study period were about 18 times more likely to experience a life-threatening event than children with no history of fainting spells in the previous ten years. Children with a recent history of a single fainting spell in the two years prior to the study period proved to be at nearly 12 time greater risk.

The second clearly identified risk factor was the length of a child's QTc, which is QT corrected for heart rate, a more accurate measure. Results confirm that patients QTc of greater than or equal to 530 milliseconds in length were twice as likely to experience a life-threatening cardiac event as those with a shorter QTc.

Thirdly, the study found that male children were at four times greater risk than females between the ages of 10 and 12, but there was no significant risk difference between males and females 13 to 20 years of age. One theory is that shifting levels of androgens in males and estrogens in females, the hormones associated with the changes of puberty, may change QTc during adolescence to create different risk levels at different stages. Further research is needed to clarify these complex relationships.

Perhaps most surprisingly, the current analysis found no significant association between the genetic type of LQTS a patient had, and their likelihood of facing a life-threatening event, despite the findings of previous publications to the contrary. The author's argue that clinical factors provide a more accurate representation of disease severity than genotype.

Lastly, researchers found that beta-blocker therapy reduced risk by 64 percent among children with syncope in the two years prior to the study period (those at highest risk). The use of beta-blockers for all LQTS patients, especially the LQT1 and LQT2 subtypes, remains prudent, according to the study authors. In addition, implantable cardioverter defibrillators (ICDs), devices designed to correct arrhythmias, should be considered given that landmark studies have found that the devices can drastically reduce sudden death.

"Between beta-blocker therapy, ICDs and preventive monitoring, we should be able to prevent many of these tragedies," said Jenny B. Hobbs, M.D., first author on the JAMA paper and a recent graduate of the University of Rochester School of Medicine and Dentistry. "Perhaps we can alleviate the suffering of these at-risk families and help to solve a major worldwide health threat with the same line of research."

Heavy Rains

Some days it still surprizes me that the sun still shines. It still snows and people still go to work. I try really hard to keep life flowing and moving in a positive direction, since I am very cognizant that my children and my husband really do look to me to set the tone with regard to our grieving. Although each person grieves differently and on a different timetable. I know that when I grieve openly, they do too and they do not function as well.
This week has been one of the hardest. I have really enjoyed having James with us, but in a sense, it opens the wound. I am very much reminded of how much we lost with Daniel's untimely passing. It makes me sad that James and Daniel have not had an opportunity to know each other here on Earth. Secondly, I had a couple of routine doctor's appointments this week and seeing them again and having them ask how I am doing induced me to answer and actually tell the truth. Lastly, I took James to a new pediatrician (better parking and hopefully fewer docs in the practice) When he told me a baseline EKG for an adolescent boy on medications was unnecessary, I wanted to punch him. Instead, I said, "Oh really ? Are you aware that both Spain and Italy do routine EKGs on all adolescents while assessing for long qt syndrome ?" I continued, "I watched my 12 year old son die in front of me, as I did CPR. I am told that it is long qt syndrome which caused this". Suffice it to say that James will be getting a baseline EKG.
The rains are heavy and there is intermittent flooding on the rural roads. The dark, cold and rainy outdoors pretty much reflect my mood.

What Really Happened to Daniel ?

Since Daniel passed, the doctors have been telling us that likely, he had an unexpected disturbance in heart rhythm and that this rhythm was incompatible with life. We are being told that there was nothing we could do to anticipate this, and that this "happens sometimes". We have not really bought this. The doctors have been focused on cardiac testing of our other children in order to prevent another such occurance, and this indeed is what has been taking our time.
When Daniel went into the bathroom, one second he was talking to us and the next, there was a gurgling sound. It was incredibly rapid, almost as you would turn a switch. When his father and I entered the bathroom, we found him on the floor, but his skin was warm and pink, not at all the way I am accustomed, as a former critical care nurse, so seeing someone in full arrest. In addition, as we turned him over (he was on his abdomen initially) his eyes were half open with one facing outward left and the other outward right. When I tried to position him for mouth to mouth and ultimately CPR, his neck was taut. Normally, a person in arrest can have their head tilted back with one hand. It was effortful for me to position him for CPR. Both his father and I believed that some type of seizure occured. The doctors were undaunted, stating that once the heart stops the brain indeed responds with seizure-like activity. Still, we wait for autopsy results while processing this terrible loss.
After Daniel died, for several days and especially during the funeral, we felt his presence. I can't be more descriptive than this, it was simply a feeling that he was with us and knew what we were doing, and wanted to be near us to comfort us. I have had some dreams where Daniel has spoken to me since, but they have been largely symbolic and brief.
On Sunday morning, the 18th, our son Matthew told us he'd had a dream. (It would actually have been on Saturday the 17th) He said that Daniel had come to him in a dream. Daniel told Matthew that he had entered the bathroom, sat on the toilet, felt nauseated, and stood and vomited in the sink. Then his vision went blurry and he passed out on the floor in front of the sink cabinet. Daniel did not think it was his heart. He told Matthew that he thought it was something in his brain. In the dream, Daniel proceeded to tell Matthew that his brain had been a great focus of the most recent part of the autopsy. He described how his brain was "cut in half" and that there had been great discussion about something that had been found in the middle of it. Daniel seemed fine and was relating this, just as he would have related an episode of Stargate. He wanted us to have this information so that we would not be quite so cardiac obsessed.
On Tuesday the 19th, we spoke on the phone to one of the pathologists who has been the liaison with us. (Normally, there is not communication with them. A report is issued to your doctor and he explains it to you.) I asked if she'd found something, and she said yes. I said, "It's neuro, isn't it ?" and she reponded, "Yes". She told us that a large pineal cyst had been found (which is located in the back center of the brain) She indicated that a pineal cyst which impedes the flow of cerebrospinal fluid and causes seizure and death is exceedingly rare, but that this is a significant abnormal finding. I told her what Daniel had Matthew on Saturday. With all the mettle a female pathologist must have, she seemed unsurprized.
With this, I began as much research on pineal cysts as possible. Small pineal cysts are a common finding on many autopsies, in fact as many as 41 %. For many people, they are completely asymptomatic, but for others, there may be intermittent headaches. Rarely, a cyst can become large enough to necessitate draining, especially if it begins to cause nausea or visual disturbances as it begins to impede cerebrospinal fluid (CSF) circulation through the ventricles of the brain. Only two other people have ever been documented to have died from a pineal cyst. When a cyst creates these cataclysmic difficulties, it is referred to as pineal apoplexy.
We are sad. We remember only twice in three months Daniel complaining of a headache. Both were when he got up in the morning. I attributed both to his allergies and gave him Claritin, but told him to let me know if the Claritin did not work. In both cases he was better in a half an hour. I now realize that these headaches may have been due to increasing intercranial pressure and that they improved only because he was up and around and had better drainage but not due to Claritin. I also now remember that he did once complain about his eyes being tired and a little blurry, but he would spend considerable amounts of time on his laptop computer, not only doing schoolwork, but creating animations, in which he was extremely gifted. I resolved to take him for an eye exam after Thanksgiving because he might need glasses, although I fully expected his eye irritation to be of allergic origin, as it is with the rest of us. I can only remember his mentioning nausea one or two times in about three months, generally when we drove in the car. He has been prone to feeling carsick all of his life. So we now begin the process of being grateful to God that Daniel does not seem to have suffered in association with his passing, and that somehow, he didn't really experience symptoms sufficient for him to alter his life, complain or worry. We never saw anything that indicated to us that anything was wrong. He was active, happy, and for two weeks I had off immediately before he died, we spent a great deal of it together. I am grateful for the time we had together but, in all, we remain heartbroken.

Note written one year later: Subsequent pathologists, on studying the autopsy data, albeit world experts on neuropathology believe that Daniel's pineal cyst, which was unruptured, was too small to have caused his death. They are still unclear on a cause of death.