International Myotonic Dystrophy Organization

The second advance that was discussed was the construction of the Myotonic Mouse Model. This model was constructed by Charles Thorton and his group in the USA. They did this by inserting CTG repeat into a mouse chromosome and thus creating DM mice. When the mice developed they have the characteristics of the disease. The breakthrough now is that there is an animal model to test potential cures for the disease! This is a very nice breakthrough for treatments in the future.

A group in Florida has identified a new protein called EXB protein. This EXB protein seems to stick to the expanding repeat and it may be the clear protein that is sticking in the cells. One large question that is trying to be answered is the reduction of this protein or others important to treating the condition.

Dr. Brooke also talked about two different type of Myotonic dystrophies

    Type I (The common form that is often discussed)
    Type II (Very Rare) This is caused by a different Gene This gene has been identified

Housekeeping Items from David Sowter

There was a request for additional skin biopsies. They took last year a lot of skin biopsies. They needed an additional 6 from volunteers.

Letter read from Dr. Peter Harper

    He was sorry he could not personally attend the meeting
    Dr. Roger Moore was going to be working with Dr. Harper
    His new book will be published next week
    He is planning on writing a smaller book for Families

Introduction of a Physician from Russia that is doing research

Dr. Mark Rogers   Clinical Management of Myotonic Dystrophy
                                 University Hospital of Wales, Cardiff

Type of Concerns are basically three:

                                Patient Concerns
                                Family Concerns
                                Dr. Medical concerns
 

Issue with Timing:

                                Immediate concerns
                                Future concerns
                                Genetic Risks-(already born, future children)

Some of the immediate concerns that were discussed were occupations at work, home adaptations. Unforeseen such as accidents and accident preventions.  A common accident is falling due to "foot drop" or weakness in the thigh muscle. There is a balance between independence and using aids such as canes and wheelchairs. Its a difficult issue "don't let the disease beat you" versus the risk of falling.

Another concern was the risk or cardiac arrhythmia's. An EEG on a regular basis was recommended. Testing should not be limited to those with obvious symptoms.

Clinical Signs and Issues

            Myotonia - Can be worse in the early years, classical symptom
            Weakness - slowly progressive can be most debilitating symptom
            Somnolence - (sleepiness) problem with people being ignorant of disease
            Speech Problems and Swallowing
            Cardiac Issues
            Breathing - can be measured, have testing done
            Bowels - high percentage of patients have these problems. Constipation or diaherrea can be 
                            serious problems. There used to be drugs that could help but the side effects were
                             sometimes worse than the treatment so the drug was discontinued.
            Cataracts - droopiness of eyelids are also a problem
            Diabetes - This disease is also abbreviated as DM can be confusing. This is an increase in  
                               insulin resistance
            Hearing - The young are prone to ear infections
            Education
            Learning Problems

Operations

            Anesthetics - avoid those that depress breathing
            Heart
            Abdominal surgery - risk of breathing problems, advise doctor recommend ICU care
            Orthopedic - falls and fractures are a problem. One major issue is the healing process with
                                    these fractures. Non affected people generally will get their muscle tone back
                                    rapidly. Those with DM have difficulty regaining the original tone. Surgeon and
                                    therapists should be aware and take appropriate actions.
            General
                        Be forward and discuss concerns with Surgeon
                        Carry a Med alert Card
                        Discuss precautions with surgeon
                        Consider donating Tissue to research, always helps
                       

Summary

            Your concerns should come first
            Doctors issues are also important
            Don't expect too much
            Dr. Moore is working with Pet   

Obesity and Myotonic Dystrophy  Dr. Ian Campbell

Overview

            Prevalence
            Effects
            Obesity and Myotonic Dystrophy
            Benefits of Weight Control
            Getting Help

WHO Classifications of weight based on BMI = Body Mass Index. BMI= weight (kg)/Height (m)2

Underweight
Healthy weight
Overweight 1
Overweight 2
morbidly Obese       

In the last 10 years in England The amount of overweight amounts has increased dramatically. For example:

The average GP has 2000 patients:

800 are overweight with a BMI of >25
320 are obese with a BMI of >30
16 are morbidly obese with a BMI of >40

Health effects

Causes of obesity are multifactor

                -genetic or Hereditary
                -dietary Intake
                 -activity levels
                -Lifestyle

One of the largest reason for the increase in obesity in the last 20 years is the level of resting activity has decreased in most people in the Western world. Activity levels have dropped. For example, the average housewife per week expended the energy of a person running a marathon 20 years ago. Now the level is substantially reduced.

Metabolic System
            Increased Insulin Resistance: This causes obesity, diabetes, High Blood pressure, high cholesterol, heart disease. It can also cause skin changes darker areas such as Acanthosis Nigricous on the groin neck and armpits. There is no treatment for this but it may suggest a risk of underlying diabetes.

Benefits of a 10% Weight Loss
            Mortality: 20% overall fall in mortality
                                30% fall in diabetes
                                40% fall in obesity related deaths
            Blood pressure fall of 10mm in systolic
            Diabetes 50% fall in sugar levels

Seeking the GP advice
            Most Gp do not know about DM (the incidence is small)
            Most GP do not know in depth about obesity
            Take someone with you to the doctor for support
            Let Doctor retain control but be proactive
            Persistence will usually pay off
            Remember you do have a choice and can choose another GP

Management of Obesity

            You must be ready to make the change
            Dietary restrictions and activity levels must work together
            " If losing weight is not the most important thing in your life stop reading now you will not be successful!"

Treatment

            Weight Loss Clinics can help
            Target 10% or .5 - 1 Kg per 3-6 weeks
            agree on a treatment, expectations, targets
            get advice on smoking, alcohol, and other issues

Dietary Adjustments

            Reduce intake by 500 kCal per day (20% reduction)
            Less fat calories should be eaten
            have a regular 3 meals per day
            Realistic sustainable advice should be sought
            Need to have a LT change in habits

Physical activity

            Recommends increased level of activity not necessarily exercise   
            Add 30 minutes of activity at least 5X per week
            walking and swimming are good activities
            watch Less TV and computer games

Behaviorisms

              Have regular meals, eat in one room, make it your sole activity (No TV)
              Medications can help if all else fails

Question from Audience:

        My daughter is 22 years old and has gained about 8 Kg in the last 8 weeks. She has not increased her rate of eating food or taking on more calories.....What should I do?

        First a comprehensive review by GP is in order to rule out any underlying problems. If there are no problems the suggestions were to increase the level of activity to help burn off some calories.

The Brain Affected Gail ? Behavioral Genetics Clinic

Early studies in the 40's and 50's showed decreases in
            Intelligence, Inactivity, apathy, and social dimensions

Psychiatric Profile

            Daytime Sleepiness
            Increased Apathy
            Depression
            possible avoidant personality

Neuropsychological

            IQ reduced
            For Congenital form some loss of Brain Tissue
            Observation of "tangles" of Brain cells in adults
            Nueroimaging  shows blood flow loss to certain areas

Social Consequences

            Reduced Education Levels
            reduced levels of Employment
            Increased levels of Poverty

Assessment
            Physical exam, blood workup, DNA for CTG(n) Psychiatric assessment
            Epworth sleepiness scale, Wechsler Intelligent Scale, Scan Wing 990
            Doors and People test
            Visual Space and Object Reception Battery (VOSP)
            Executive Functioning/MRI
                        They looked at MRI in sections and where able to measure the level of chemicals in the brain. Based on the levels of chemicals this gives the researchers and idea of the level of activity.

Gail ? Group Research Study preliminary result based on small sample size:

IQ was within normal range
Memory within a normal range
Language skills Normal range
Front Lobe Variable
apathy Scale Slightly increased apathy
sleepiness Abnormal
health + Fatigue Increased tiredness and weakness, decreased energy
General Health abnormal social dysfunction
Anxiety and Depression Variable

Sleep and Sleep Apneas

Dr. Margaret Philips Based in Darby

Definitions from Audience
    Absolutely shattered, can't keep my eyes open, exhausted, lack of energy, knackered, drop off, tired

Medically
            Muscle Fatigue: reduced ability to do work but can recover ability after a rest
            Central Fatigue: low motivation, boredom, lack of attention
            Sleepiness: Overwhelming urge to sleep during the day

Relevance of words:
            Judge the specific problem of a person
            helps direct the investigation of problems
            research may help us

What contributes to sleepiness?
            sleep disorder breathing
            poor respiratory functions
            depression
            control of sleep

Sleep Disorder Breathing
            Sleep is complex, brain controls breathing during sleeping. REM sleep is when dreaming occurs. when sleeping the muscles relax and this may cause issues. Laying down alters the way we breath, makes it harder to breathe,

Patients with DM
            Control of Sleep: The way the brain controls sleep  and breathing are different in DM
            Respiratory Muscles are weaker
            Some patients have smaller jaws
            Muscles around the pharynx and larynx are weaker
            Some people are overweight.

Sleep Apnea
            defined as a breath not taken for 10 seconds or more during sleep
            If this happens often the quality of sleep is poor
            Common and occurs without other medical problems

Treatment
            Makes upper Airway open, weight loss
            If small jaw an appliance can be used
            Non-Invasive intermittent BiPAP or NIPPV can be used. This is a machine that is used while    sleeping to help prevent the sleep apnea.

Question: I seem to have erratic sleeping patterns and sleep during day and am awake at night?

                    Suggestions of keeping active. Others in the room agreed with this assessment. One gentleman mentioned he was taking provigil and that this help a lot with sleeping during the day and night.

Sleep Problems:

            Lack of social contacts, work problems, boredom, concentration and care of young children, people tell you to wake up, stand up straight, tell you to get going in the morning, can not see the end of a film, people do not recognize sleeping problems, called "Lazy" especially children at school. There are ongoing trails with Modafinal by Dr. Hilton-Jones. This was the sleeping drug suggested last year.

Panel Discussions
All speakers plus Family Care Coordinators

Q1: I seem to have hiccups that are uncontrollable
A: Polled the group of 200 no one seems to have this problem or issue
 

Q2: Woman said that her daughter had seizures, how can she help?
A: the panel made an important point here which they emphasized later. People with Dm are not immune to other diseases and symptoms. That means that it is likely that people with DM will have other diseases and not all symptoms can be linked to DM. There is a tendency in patients to make the association that all of their symptoms are related to DM. Seizures are not associated with DM and they should be treated separately.

Q3: Are there any therapies to prevent Cataracts?
A: There is nothing that the panel is aware of to prevent Cataracts.

Q4: My daughter and husband are underweight and thin what can be done?
A: Underweight can be moderate to severe and can be caused by swallowing problems. There may be other eating problems. Some people will be thinner than others. If we exclude endocrine problems this can be DM related. Need to insure proper eating and that correct type of foods that are easy to swallow are taken. Additionally, further testing of the GI tract may need to be done.

Q5:My Husband had cataract surgery under anesthetic, My daughters doctor does not want to use anesthetics. I am concerned about the use of anesthetics...
A: This is difficult to give specific advice. Generally the physician will assess the situation and give their best advice and direction. You may want to discuss the use of antics again with the doctor.

Q6: I have trouble getting up in the morning
A: This can be both psychological and physiological. There is excessive sleepiness especially with the adult onset. We don't know why but it is probably a brain problem, the brain for some reason needs or directs more sleep. If you feel groggy in the morning make sure there are no extra problems. Might need to go to a sleep clinic for evaluation.

Q7: I have a 12 year old son who is active and does not seem affected. Should he be tested?
A: Genetically there is a 50-50 chance of any individual having the disease. There is a feeling that individuals have a right to be tested or not. If there is not overriding reason for testing it should not be done.

Q8: Mechanism of action for the proposed MRNA. IS the Mechanism of action because the MRNA is trapped in the cell and "poisons' It or is the Mechanism of action because the MRNA can not escape the nucleus and make the appropriate protein
A: Good question we do not know the exact Mechanism of action.

Q9: I have had some problems with food objects sticking in my throat when swallowing. Several others reported the problem when the room was polled.
A: DM affects the smooth muscle and could cause this issue. There are diagnostic techniques such as swallowing a liquid that can be seen on an X-Ray to see if there is an area of concern. Has had severe pain as swell as taken a gut relaxer to try and improve condition. On a few occasions she was unable to eat or drink for 3 days.

Q10: Both   myself and my son have a scaly condition of the skin what can be done to improve this?
A: Various creams can be used  but nothing has been successful. These creams may be able to give temporary relief.

Q11: Is impotence related to problem of DM?
A: Yes, there are a lot of reasons why. Impotence may be psychologically related. In DM the testicles may be smaller and produce=duce less testosterone. The parasympathetic nerves may be affected and the smooth muscles and blood vessels are affected. These areas are important for men to achieve rejections. Diabetes is also associated with Impotence. So there can be a variety of physical and psychological reasons.

Q12: My son seems to be choking on foods. HE is 9 years old
A: Seems as though the food is getting stuck in the food pipe. They recommended that he be seen by a speech and swallowing expert.

Q13: How common is DM and MS in the same family?
A: These are two know diseases with known probabilities and incidences. There is no information that links the two so you can compute the probabilities of having both at the same time. This is probably just a coincidence.

Q14: Will Dr. Marin X, and Dr. Brooke continue doing collaborative Research?
A: The teams have had similiar lines of investigations for 7-8 years on a collaborative grant. Universities like to create critical masses which tends to collorilete with breakthroughs. They will continue to work on similiar and also different work. For example. Marian Hanshere is developing a worm model which would be a more simple model to make studies with./ This is a simple nematode worm.

Q15: Can a women with Myotonic dystrophy have preimplanation testing before implantation?
A: This deals with embryo implantation. There is one center in the UK where preimplanation wok is done. They then fertilize the eggs and then implant into the women. The embryo is at the 12-16 cell stage at this point. 4 cells go to make the baby and 8 cells to make the placenta. 1 cell is removed to test for the expanded CTG repeats. Weiss Hospital in London will perform this under the NHS. But the Local Health authority will have to pay for this on a regional basis.

Again, as before the formal conference was over all too soon.  We did have lots of time that evening and into the next morning to talk and chat. To share experiences and helpful hints. All too soon we were off on the Bus, back to London and Back to Chicago USA home! My thanks again to the committee members and the members of the MDSG who gave us such a warm and friendly welcome.