Excerpt from http://www.medicinenet.com/gastroesophageal_reflux_disease_gerd/article.htm

What is GERD (acid reflux)?

Gastroesophageal reflux disease, commonly referred to as GERD, or acid reflux, is a condition in which the liquid content of the stomach regurgitates (backs up, or refluxes) into the esophagus. The liquid can inflame and damage the lining of the esophagus although this occurs in a minority of patients. The regurgitated liquid usually contains acid and pepsin that are produced by the stomach.  Acid is believed to be the most injurious component of the refluxed liquid.

GERD is a chronic condition. Once it begins, it usually is life-long. If there is injury to the lining of the esophagus (esophagitis), this also is a chronic condition. Moreover, after the esophagus has healed with treatment and treatment is stopped, the injury will return in most patients within a few months. Once treatment for GERD is begun, therefore, it usually will need to be continued indefinitely.

Gravity, swallowing, and saliva are important protective mechanisms for the esophagus, but they are effective only when individuals are in the upright position. At night while sleeping, gravity is not in effect, swallowing stops, and the secretion of saliva is reduced. Therefore, reflux that occurs at night is more likely to result in acid remaining in the esophagus longer and causing greater damage to the esophagus.

The symptoms of uncomplicated GERD are primarily heartburn, regurgitation, and nausea. Other symptoms occur when there are complications of GERD and will be discussed with the complications.

Heartburn

When acid refluxes back into the esophagus in patients with GERD, nerve fibers in the esophagus are stimulated. This nerve stimulation results most commonly in heartburn, the pain that is characteristic of GERD. Heartburn usually is described as a burning pain in the middle of the chest. It may start high in the abdomen or may extend up into the neck. In some patients, however, the pain may be sharp or pressure-like, rather than burning.  In other patients, the pain may extend to the back. Since acid reflux is more common after meals, heartburn is more common after meals. Heartburn is also more common when individuals lie down because without the effects of gravity, reflux occurs more easily, and acid is returned to the stomach more slowly.

Episodes of heartburn may occur infrequently or frequently, but episodes tend to happen periodically. This means that the episodes are more frequent or severe for a period of several weeks or months, and then they become less frequent or severe or even absent for several weeks or months. Nevertheless, heartburn is a life-long problem, and it almost always returns.

Regurgitation

Regurgitation is the appearance of refluxed liquid in the mouth. In GERD, usually only small quantities of liquid reach the esophagus, and the liquid remains in the lower esophagus. Occasionally, and particularly in some patients, larger quantities of liquid, sometimes containing food, are refluxed and reach the upper esophagus.

What's more, frequent or prolonged regurgitation can lead to acid-induced erosions of the teeth.

Nausea

Nausea is uncommon in GERD. In some patients, however, it may be frequent or severe and may result in vomiting. In fact, in patients with unexplained nausea and/or vomiting, GERD is one of the first conditions suspected. It is not clear why some patients with GERD develop mainly heartburn and others develop mainly nausea.

Ulcers

The liquid from the stomach that refluxes into the esophagus damages the cells lining the esophagus. The body responds in the way that it usually responds to damage, which is with inflammation (esophagitis). The purpose of inflammation is to neutralize the damaging agent and begin the process of healing. If the damage goes deeply into the esophagus, an ulcer forms. Ulcers and the additional inflammation they provoke may erode into the esophageal blood vessels and give rise to bleeding into the esophagus.

Strictures

Ulcers of the esophagus heal with the formation of scars (fibrosis). Over time, the scar tissue shrinks and narrows the lumen (inner cavity) of the esophagus. This scarred narrowing is called a stricture. Once the narrowing becomes severe enough (usually when it restricts the esophageal lumen to a diameter of one centimeter), swallowed food may get stuck in the esophagus. This situation may necessitate endoscopic removal of the stuck food. Then, to prevent food from sticking, the narrowing must be stretched (widened). Moreover, to prevent a recurrence of the stricture, the reflux also must be prevented.

Barrett's esophagus

Long-standing and/or severe GERD causes changes in the cells that line the esophagus. These cells then become pre-cancerous, and finally cancerous. This condition is referred to as Barrett's esophagus, which occurs in approximately 10% of patients with GERD. The type of esophageal cancer associated with Barrett's esophagus (adenocarcinoma) is increasing in frequency.  It is not clear why some patients with GERD develop Barrett's esophagus, but most do not.

Cough and asthma

Many nerves are in the lower esophagus. Some of these nerves are stimulated by the refluxed acid, and this stimulation results in pain (usually heartburn). Other nerves that are stimulated do not produce pain. Instead, they stimulate yet other nerves that provoke coughing. In this way, refluxed liquid can cause coughing without ever reaching the throat! In a similar manner, reflux into the lower esophagus can stimulate esophageal nerves that connect to and can stimulate nerves going to the lungs. These nerves to the lungs then can cause the smaller breathing tubes to narrow, resulting in an attack of asthma.

So, GERD is a common cause of unexplained coughing. Although GERD also may be a cause of asthma, it is more likely that it precipitates asthmatic attacks in patients who already have asthma. Although chronic cough and asthma are common ailments, it is not clear just how often they are aggravated or caused by GERD.

Inflammation of the throat and larynx

If refluxed liquid gets past the upper esophageal sphincter, it can enter the throat (pharynx) and even the voice box (larynx). The resulting inflammation can lead to a sore throat and hoarseness. As with coughing and asthma, it is not clear just how commonly GERD is responsible for otherwise unexplained inflammation of the throat and larynx.

Inflammation and infection of the lungs

Refluxed liquid that passes the larynx can enter the lungs. The reflux of liquid into the lungs (called aspiration) often results in coughing and choking. Aspiration, however, can also occur without producing these symptoms. With or without these symptoms, aspiration may lead to infection of the lungs and result in pneumonia. This type of pneumonia is a serious problem requiring immediate treatment. Aspiration is more likely to occur at night because that is when the processes (mechanisms) that protect against reflux are not active and the coughing reflex that protects the lungs also is not active.

Fluid in the sinuses and middle ears

The throat communicates with the nasal passages. In small children, two patches of lymph tissue, called the adenoids, are located where the upper part of the throat joins the nasal passages. The passages from the sinuses and the tubes from the middle ears (Eustachian tubes) open into the rear of the nasal passages near the adenoids. Refluxed liquid that enters the upper throat can inflame the adenoids and cause them to swell. The swollen adenoids then can block the passages from the sinuses and the Eustachian tubes. When the sinuses and middle ears are closed off from the nasal passages by the swelling of the adenoids, fluid accumulates within them. This accumulation of fluid can lead to discomfort in the sinuses and ears. Since the adenoids are prominent in young children, and not in adults, this fluid accumulation in the sinuses and ears is seen in children and not adults.

There are several ways to approach the evaluation and management of GERD. The approach depends primarily on the frequency and severity of symptoms, the adequacy of the response to treatment, and the presence of complications.

For infrequent heartburn, the most common symptom of GERD, life-style changes and an occasional antacid may be all that is necessary. If heartburn is frequent, daily non-prescription-strength (over-the-counter) H2 antagonists may be necessary. A foam barrier also can be used with the antacid or H2 antagonist.

If life-style changes and antacids, non-prescription H2 antagonists, and a foam barrier do not adequately relieve heartburn, it is time to see a physician for further evaluation and to consider prescription-strength drugs. The evaluation by the physician should include an assessment for possible complications of GERD based on the presence of such symptoms or findings as cough, asthma, hoarseness, sore throat, difficulty swallowing, unexplained lung infections, or anemia (due to bleeding from esophageal inflammation or ulceration).

If there are no symptoms or signs of complications and no suspicion of other diseases, a therapeutic trial of acid suppression with H2 antagonists often is used. If H2 antagonists are not adequately effective, a second trial, this time with the more potent PPIs, can be given. Sometimes, a trial of treatment begins with a PPI and skips the H2 antagonist. If treatment relieves the symptoms completely, no further evaluation may be necessary and the effective drug, the H2 antagonist or PPI, is continued. As discussed above, however, there are potential problems with this commonly used approach and some physicians would recommend a further evaluation for almost all patients they see.

If at the time of evaluation, there are symptoms or signs that suggest complicated GERD or a disease other than GERD, or if the relief of symptoms with H2 antagonists or PPIs is not satisfactory, a further evaluation by endoscopy (EGD) definitely should be done.

There are several possible results of endoscopy and each requires a different approach to treatment. If the esophagus is normal and no other diseases are found, the goal of treatment simply is to relieve symptoms. Therefore, prescription strength H2 antagonists or PPIs are appropriate. If damage to the esophagus (esophagitis or ulceration) is found, the goal of treatment is healing the damage. In this case, PPIs are preferred over H2 antagonists because they are more effective for healing.

If complications of GERD, such as stricture or Barrett's esophagus are found, treatment with PPIs also is more appropriate. However, the adequacy of the PPI treatment probably should be evaluated with a 24-hour ph study during treatment with the PPI. (With PPIs, although the amount of acid reflux may be reduced enough to control symptoms, it may still be abnormally high. Therefore, judging the adequacy of suppression of acid reflux by only the response of symptoms to treatment is not satisfactory.) Strictures may also need to be treated by endoscopic dilatation (widening) of the esophageal narrowing. With Barrett's esophagus, periodic endoscopic examination should be done to identify pre-malignant changes in the esophagus.

If symptoms of GERD do not respond to maximum doses of PPI, there are two options for management. The first is to perform 24-hour ph testing to determine whether the PPI is ineffective or if a disease other than GERD is likely to be present. If the PPI is ineffective, a higher dose of PPI may be tried. The second option is to go ahead without 24 hour ph testing and to increase the dose of PPI.

Patients should consider surgery if they have regurgitation that cannot be controlled with drugs. This recommendation is particularly important if the regurgitation results in infections in the lungs or occurs at night when aspiration into the lungs is more likely. Patients also should consider surgery if they require large doses of PPI or multiple drugs to control their reflux. Still, it is debated whether or not a desire to be free of the need to take life-long drugs to prevent symptoms of GERD is by itself a satisfactory reason for having surgery.

Circle of Friends

Shanelle McGloin, Age 7

    When I read about the families on here and the problems and illnesses they battle with, I feel a little silly for worrying so much about Shanelle, but also very lucky that we are fortunate that she doesn’t have any serious illness. However I do still worry as I guess all families do. She has just had her annual review at school, and even though there is improvement, its also disheartening sometimes. Activities are hard for her, as she has weakness of shoulder and pelvic stability, so she slouches and sits funny. She has trouble with co-ordination, and weakness in her grip strength.

   For the past year, I have been really concerned because she would get the same kind of homework every week. Writing tasks, asking her to copy letters, or write small words like 'cat'. She could never do any of these and the teachers were aware of my concerns. Anyway after finally getting a proper assessment by an occupational therapist, they have finally realized that because of her problems, she is unable to write anything for the time being. The school have applied for a personal laptop for her to record all her work. I am thrilled about that, it was upsetting to have her keep trying the same things that she was just unable to do.

   She also had a 'Visual perception skills test', which tested her on many different things. There was 6 parts to the test, and she got 1 percent in every one. This placed her below the first percentile which is quite upsetting too. Her lack of concentration is a big, big problem. It is impossible to talk to her properly because she goes off mid-sentence and talks about something completely different, cannot sit still for long, and just gets bored very easy. She sometimes repeats things over and over again, even if I answered her the first time, and I just really feel for her (even though it drives me mad. LOL).

   The best thing is her health has been good for a long time, not many chest infections or asthma attacks. She has got an operation coming up to have a growth removed on her foot, I cant remember the name, although the doctors were surprised because this problem is normally noticed in people over the average age of 40!! Something to do with trauma of the foot which made no sense either but never mind!!

   All these concerns are just me being motherly.  Shanelle doesn’t seem phased by any of it. She’s a happy soul with lots of love to give and she is my angel.

   I just felt like writing because this is the only place I can let of a bit of steam, as no-one knows or has heard of CLS.

   God bless you and your families.

~ 

Andrew Anderson, Age 18

    I heard from one of Andrew's doctors and got some bad news. His MRI shows the problem of the white matter "lighting up" which means that his brain tissue is deteriorating (dying). I haven't heard from the neurologist or orthopedic doctors yet. For now I'm left wondering what is going to happen to Andrew and how soon anything will happen. It has been bad enough that Andrew is no longer able to even sit up or walk with no support. He has regressed from minimal assistance for his daily activities to total dependence for everything, all just since March of this year (2005). I am wondering if any other kids have experienced this. I am very worried that Andrew will not be with us much longer if it continues and what surgery is supposed to keep his brain from dying. The doctor wouldn't go into any more detail considering she is a general practitioner and not the specialist.

   Other than that we are all doing great. We have moved back to California after living in Alabama for just over a year and a half. We now live in Mariposa which is about 45 minutes from Yosemite Nt. park; one of Andrew's favorite places! He is still in high school and doing well as can be expected with all his changes. We have had some problems getting his needed services since we are in a small mountain community. I started working on everything way back in February and Andrew has just recently started getting things. He is incontinent so he receives briefs, wash and lotion. He has a rented wheel chair for now. It reclines so that he can sit comfortably. His appointment for a therapy review is the first of February 2006 so he will receive his permanent one soon after that. We will also be purchasing Andrew a recliner for the house, since all he can do for comfort is lay down. He spends most of his time laying on the floor.  Andrew uses a big pillow for the floor, which we are replacing with tumbling mats soon. He also uses memory foam for his bed. Unfortunately we still have problems with Andrew getting pressure sores on his hips and tailbone areas. I have been able to take care of them since I am a CNA; I have learned what to do to help the sores heal or not happen at all. sometimes they just happen fast though. 

~

Ashley Hayden, Age 20

    My daughter is currently seeing a fine neurologist and psychologist; however neither of these professionals has ever had a patient with Coffin-Lowry Syndrome or actually had ever heard of it prior to meeting our daughter.  Ashley is currently being treated for depressive psychosis and our neurologist has continued to try several seizure medications to try to lesson the symptoms of her drop attacks and startles, but so far to no avail.  He told us at our most recent appointment that he had one more med to try and then he absolutely was at the end of his ideas.  He said that there was a doctor in Cincinnati, OH that was a specialist in pediatric movement disorders, but he felt sure that he wouldn't have any other ideas.   

   My husband and I were wondering if there are any doctors anywhere that have more experience with CLS?  We are just so saddened to see the decline in our daughter.  Just 2 - 3 years ago, she was participating in Special Olympic basketball, ice skating and bowling.  She is now unable to walk on her own, and is so uncomfortable and anxious in her wheel chair that her activities are so limited. Also, she no longer can sit in a regular chair without great anxiety.  That has prohibited her from attending the water aerobics class that she once enjoyed as well as sitting in church, going to the movies etc.  

   We know that if she is not able to exercise, other health problems will occur.   Therefore, I would like to know of any medical professional that might be familiar with CLS or it's symptoms that might have more information.  Is there anyone doing any medical trials or studies that we could be a part of for further knowledge? 

   Also, has anyone found any special equipment, OT, PT or exercise plans that have been effective, please share that as well. 

   Thank you sincerely for your time and interest in this request.  

Genes defective in rare disease help form bones

 From a press release by Kate Ramsayer dated April 29, 2004.

 http://www.bcm.edu/fromthelab/vol03/is4/04may_n3.htm. 

    The short stature and brittle bones that worsen over time in patients with Coffin-Lowry Syndrome are the result of a defective protein that the production of new bone tissue, according to researchers Baylor College of Medicine in Houston.

   In a paper published in the April 30 issue of Cell, scientists follow the path of missteps in this rare disease, from the gene that is mutated in people, to an intermediate protein that should be activated, to the failure of the bone-forming cells called osteoblasts to do their job.

   “The disease we were looking at, Coffin-Lowry Syndrome, was known to be due to a mutation in the kinase called RSK2,” said Gerard Karsenty, MD, PhD, a BCM professor in the department of molecular and human genetics. A kinase is a protein that adds a phosphate group to another protein, often switching it to an active form. “What was not known was how the kinase was causing either the mental retardation or the skeletal abnormalities of the patients.”

   Karsenty and his colleagues discovered that one of the proteins activated by RSK2 is called ATF4. They conducted a series of experiments in cell cultures and in mice to examine the effect of RSK2 and ATF4 on bone formation. Like patients with Coffin-Lowry Syndrome, mice lacking RSK2 had shorter, less dense bones and bigger gaps between the skull fragments at birth.

   Mice lacking ATF4 had similar but more severe deformities. Many die at birth; possibly because their bones are so brittle that they are crushed. Within their bones, these mice have thinner, shorter, fewer of the bone tissue strands called trabeculae.

   When they conducted experiments in the bone-forming osteoblast cells to determine why this happened, Karsenty and his colleagues found that cells lacking ATF4 are slower to differentiate and become mature osteoblasts. In addition, these could not produce sufficient Type I collagen, which is the main component of bone.

   “This explains why the symptoms of the disease worsen over time,” said Karsenty. “The patient progressively makes less and less collagen, and the bone degenerates more and more.”

   Scientists knew that ATF4 normally transports amino acids, the building blocks of proteins, into the cell. If osteoblasts don’t produce collagen in Coffin-Lowry patients because ATF4 is not importing amino acids, this could lend itself to a simple clinical treatment, said Karsenty.

   “By giving patients a diet rich in protein, one could try to see if it corrects or rescues the skeletal manifestations,” he said. His lab is currently trying this in mice, while his European colleagues are conducting clinical trials in people.

~ 

   Work performed in the laboratories of several members of The Bone Disease Program of Texas is defining important steps in the regulation of bone osteoblast (bone-forming cells) development and function:

“Learning and Memory”

This article covers Coffin-Lowry syndrome, Neurofibromatosis and Rubenstein-Taybi. It explains the cellular level mechanism behind the learning difficulties associated with CLS, and why people with CLS may be prone to anxiety and panic attacks. Thanks to Suzanne Solorio for finding both this article and the one to the left. http://www.scielo.br/pdf/rbp/v26n3/en_a11v26n3.pdf

Thanks for Caring!

The following families or individuals have recently made generous donations to the Coffin-Lowry Syndrome Foundation:

Send your donations to:  

Coffin-Lowry Syndrome Foundation

c/o Mary Hoffman

3045 255th Ave SE

Sammamish, WA 98075 

(U.S. Funds, please)

For a donation of $50 or more, you may request to receive a set of five beautiful hand-made greeting cards - simply write "Cards" on your check. The cards are made with exotic papers and mizuhiki cord embellishments. No two are exactly alike. Click here for full-color samples.

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