Community members discuss daily living strategies for motivating their adult children living with juvenile-onset DM1.
Please note: This is an audio recording only. To view the accompanying presentation, please click here.
Community members Penni Warford, Sarah Clarke and Ann Spaulding discuss best practices for planning and implementing your child's Individualized Education Plan.
This is an audio recording only. To see the handout that accompanied this presentation, please click here.
Dr. Craig Campbell, MD, of Western University in Ontario, Canada, has a discussion with audience members about congenital DM. In the video, Dr. Campbell does not follow a set slide show, but he created slides for additional viewing information. Please click here to see his slides.
Community-led session led by Sarah Berman, Erica Kelly, and Catherine Wycoff, DPT, GCFP, ABMCP. Parents of children living with DM and a hippotherapy specialist discuss the benefit that this type of therapy can often have.
The Myotonic Dystrophy Family Registry currently has over 1,900 participants, making it one of the largest and most up-to-date myotonic dystrophy (DM) registries in the world. If you’ve been diagnosed with DM1 or DM2, including congenital or juvenile onset, or are the primary caregiver for some who has, and you haven’t already joined the Registry, we need you!
By participating in the Registry you can help researchers from industry and academia identify potential clinical trial participants and research study subjects, and increase understanding of the impact and complexity of this disease.
The Registry is patient-driven, which means you’re in charge of your information. You can opt out of the Registry at any time, and you can also visit the Registry website to review de-identified (anonymous) data and information the same way that registered researchers do. Your individual information is kept completely confidential. Data in patient registries is typically considered out of date and less useful if it is not updated at least every 18 months, so we’ll remind you to log back into the Registry to review and update your survey occasionally.
Click here to go to the Registry website, read and sign the consent form, and get started.
Questions? Contact the Registry Coordinator for more information.
Dr. Katharine Hagerman, Research Associate at Stanford University Neuromuscular Division and Clinics, has prepared the following summary of the recently published study, "Parental Age Effects, But No Evidence for an Intrauterine Effect in the Transmission of Myotonic Dystrophy Type 1" in the Journal of Human Genetics.
Researchers from the laboratories of Fernando Morales from the University of Costa Rica, and Darren Monckton from the University of Glasgow collaborated in a recent study examining how the DNA mutation causing myotonic dystrophy type 1 (DM1) worsens from one generation to the next. Previous studies have shown that the DM1 mutation behaves differently depending on whether it is passed on from the father or mother. However, there has been conflicting information regarding whether the age of the parent’s symptom onset or parent’s age at conception of their affected child can change the degree to which the child is affected by DM1.
The conflict in research findings is likely the result of using different methods to assess the size of the DM1 mutation, and failing to account for the age of the parent at the time the blood was collected, since the mutation grows throughout their lifetime. This study uses a newer technique called "small pool PCR" to assess the mutation size, and a complex statistical analysis to predict what the original size of the repeat was at birth. This method clarified the relationship between parent and child with regard to CTG repeat size and symptom onset, confirming that children born with DM1 have an inherited repeat that is larger than their parent’s repeat about 95% of the time, and symptom onset comes earlier in the child than their affected parent around 86% of the time. Furthermore, the parent’s age of onset is correlated with the child’s age of onset, but the correlation is much stronger in affected mothers than fathers.
What really stood out in this paper was a completely new finding that the age of the affected parent at conception correlates with the repeat size in their child. In other words, as people with DM1 age, the size of the repeat in their eggs or sperm grows larger. Basic genetic principles dictate that there is a 50% chance of an affected parent passing on the mutation to their child.
This paper found that if the child inherits the mutation from their mother and gets DM1, there is a 64% risk of the child’s DM1 being congenital if the mother’s repeat size is above 164 CTGs. There are very few cases of an affected father having a congenitally affected child, and none were found in this study. Unfortunately, current procedures for diagnosing DM1 do not use the same experimental method as in this paper and do not predict what the individual’s repeat was at birth. Therefore this predicted risk cannot be applied to mothers whose repeat was sized using conventional methods for diagnosis.
The authors estimate that the diagnostic test most women get to determine the size of their repeat would also predict that if their offspring inherit the expanded repeat, they would be congenitally affected 64% of the time when the mother's repeat length is over 284 CTGs.
Genetic counseling for families with DM1 can be very complicated, as many factors such as the repeat size and sex of the DM1-affected parent can alter any predictions as to how severely a child may be affected. Overall, this study clarifies how the growing repeat size in adults with DM1 can affect their children, and brings to light a new factor to be considered by genetic counselors when advising families of the risks of transmitting DM1.
Click here to view the article abstract. Click here for an interview on genetic counseling with Carly Siskind of Stanford University Hospital and Clinics.
08/20/2014
Both DM1 and DM2 are passed from parent to child by autosomal dominant mutations. This means that the faulty gene is located on one of the chromosomes that does not determine sex (autosome) and that one copy of the mutated gene is enough to cause the disease (dominant). Because the gene is not located on the X or Y sex chromosomes, it can be passed to male and female children with equal frequency.
In nearly all cases, patients with DM have one normal copy of the DM gene and one copy with the mutation. This means an affected parent has a 50% chance of passing on the mutated gene to an offspring. Individuals who receive the mutated gene will have the disease, although they may not show symptoms for many years. Children that do not inherit the mutated gene will never develop DM.
A recent study suggested that all affected individuals can be traced back to just one or two people who had the original mutations, thousands of years ago. Unlike some genetic diseases (e.g. the types caused by exposure to toxic chemicals or radiation), the mutations causing DM do not occur spontaneously.
This webinar is presented by a group of moms offering their knowledge and experience raising children with congenital DM. This webinar includes informed, practical suggestions from alleviating gastro-intestinal challenges with proper diet and natural supplements to advocating for your child's Individualized Education Program (IEP).
To support our commitment to research, MDF awards fellowship grants to postdoctoral researchers as part of our annual Fund-A-Fellow (FAF) program. We recently caught up with one of our current grant recipients, Dr. Nicholas Johnson, Assistant Professor of Neurology at the University of Utah.
Dr. Johnson was inspired to focus his practice and research on myotonic dystrophy after working for five years at the University of Rochester with Dr. Chad Heatwole, Dr. Richard Moxley, Dr. Charles Thornton and a number of other clinicians and researchers leading the charge to find new treatments and cure for DM. He opened his practice at the University of Utah in July of 2013 and is excited to be able to treat the large DM population in Utah and surrounding states.
“There is an excellent neurology department at the University of Utah,” Dr. Johnson says, “but previously no one was focused specifically on researching DM. Being here gives me the opportunity not only to provide ongoing treatment to those individuals, but to include many of them in our research studies as well, which is exciting.”
We spoke with Dr. Johnson about his current FAF research.
NJ: “Sure. Once I received the FAFA grant, I began a project in March 2012 to develop a tool that can be used in a clinic or in research studies to measure how myotonic dystrophy impacts the quality of life of a child with congenital or childhood-onset DM.
“The tool is called Congenital and Childhood Myotonic Dystrophy Health Index or CCMDHI. It’s a survey-based tool that collects data about quality of life from birth to age 18. Until now, there’s been very little data about how DM progresses from birth to adulthood, but that information is necessary for clinical trials to move forward.”
NJ: “We interviewed 32 children and 12 parents and created the survey with their direct quotes so we could compare how their symptoms might impact the larger DM population’s quality of life. The survey was then sent out via the Myotonic Dystrophy Family Registry, the National Registry for DM and FSHD at Rochester, and the Canadian Neuromuscular Disease Registry, as well as via Dr. Anne-Berit Ekstrom of Sweden, who takes care of a large population of Swedish patients with congenital or childhood DM.
“One of the salient discoveries was that there was more than expected cardiac issues reported in children when we asked parents about comorbidities. Another interesting result was that 20-30% reported ADHD or autism symptoms.
“Of children over 18 years old, 86% were unemployed, which is pretty significant and tells us that there are a lot of ongoing issues and we need to emphasize social support when we take care of these patients. Communication problems are a huge issue. Reports of fatigue and difficulty with mobility were also reported.
“Importantly, reported symptoms seemed to vary between birth and age 18 and over. Issues for those with young children were very different from those with older teenage children. And all children were very different from the experience of adult onset DM. Parents reported significantly more communication problems, as well as emotional and social issues. On the upside, there were less myotonia and pain symptoms in the children.”
NJ: “Now that we have a preliminary instrument, we’re finishing testing and will be moving on to our next study. I’ll be working with a research team here at the University of Utah on a study called ‘Health Endpoints and Longitudinal Progression in Congenital Myotonic Dystrophy’ or HELP CDM.
“This study, which is funded by MDA, is expected to start in January 2014 and will validate CCMDHI while helping find other endpoints that will be important in clinical trials.
“During the study, children from birth to 13 years old will come in for a variety of testing, including strength and functional testing, speech and swallow testing, neuropsychological testing, and respiratory and cardiac testing. Sixty children with congenital DM, who are currently being treated here at the University of Utah and also at and University of Western Ontario, will be measured. Ultimately, we hope this will allow us to transition to successful trials and therapies for the pediatric population.
“Separately, we’ve partnered with MDF to send out a survey via the Myotonic Dystrophy Family Registry to see how women with DM are affected during pregnancy and whether symptoms improve or worsen. That survey will be going out soon. Previously, researchers have looked at complications that can occur during pregnancy but not how quality of life is impacted as a result.”
NJ: “The Myotonic Dystrophy Family Registry established by MDF and the National Registry for Myotonic Dystrophy at the University of Rochester have been instrumental in recruiting patients for our upcoming HELP CDM study. I mentioned that we’re also using these registries to conduct a number of surveys that will provide us with data we need to keep research moving forward. I encourage everyone to sign up, if they haven’t already. It really does make a difference.”
12/18/2013
Nicholas Johnson, MD, and researchers at the University of Rochester recently published an article in The Journal of Child Neurology that describes the impact of childhood and congenital myotonic dystrophy on quality of life. The authors interviewed 21 children with childhood and congenital myotonic dystrophy and 13 parents. After recording these interviews, the authors reviewed transcripts to identify the most important symptoms to parents and children. Overall, participants reported 189 different symptoms.
Dr. Johnson and his colleagues found that many of the parents and children identified trouble speaking (dysarthria) as the primary symptom that impacted the children’s lives. Other participants identified learning difficulties and problems concentrating as life altering symptoms. Although many of the study participants did not identify a diagnosis of autism specifically, autistic traits, such as a narrow scope of interest, repetitive speech, inappropriate social responses, and inflexibility were reported.
As expected, many of the symptoms affecting those with congenital and childhood myotonic dystrophy are different from the symptoms of adult-onset myotonic dystrophy type-1. Prior work by Chad Heatwole, MD, MS-CI, the senior author on this study, identified fatigue, hand and finger weakness, and difficulty walking as significantly impacting the quality of life of those with adult-onset myotonic dystrophy type-1. While these symptoms were also reported in children with myotonic dystrophy, their presentation and significance were different.
Importantly, many symptoms of congenital and childhood myotonic dystrophy, such as communication difficulties, already have available treatments. The authors hope that by identifying the wide range of symptoms affecting children with myotonic dystrophy, doctors will be able to identify critical symptoms earlier and initiate timely treatment strategies.
Dr. Johnson and University of Rochester researchers, with the support of MDF, have used information from this study to develop a survey, which was distributed to US, Canadian and Swedish patients with congenital and childhood myotonic dystrophy. Results from this international group of patients will be used to further define and prioritize the most important symptoms to patients with congenital and childhood myotonic dystrophy. Ultimately this data will be used to help guide researchers in designing future therapeutic trials for these populations.
06/25/2013