|
|
| DiseaseID |
HGD54 |
| Genetic
Disorder |
Myotonic Dystrophy
|
| Gene
Name |
dystrophia myotonica-protein kinase |
| Description |
Myotonic dystrophy (DM) is a chronic, slowly progressing, highly variable inherited multisystemic disease that can manifest at any age from birth to old age. It is characterized by wasting of the muscles (muscular dystrophy), posterior subcapsular iridescent cataracts (opacity of the lens of the eyes), heart conduction defects, endocrine changes and myotonia (difficulty relaxing a muscle). Most notably, the highly variable age of onset decreases with successive generations. Thus the disease shows at an earlier age in successive generations, a phenomenon termed anticipation. There are two classifications of DM, each having different associated symptoms.
|
| Symptoms |
Presentation of symptoms varies considerably by form (DM1/DM2), severity and even unusual DM2 phenotypes. DM1 patients often present with myotonia, disabling distal weakness and severe cognitive problems. DM2 patients commonly present with muscle pain, stiffness, fatigue, or the development of proximal lower extremity weakness (Day & al, 2003). The characteristic pattern of weakness is different for DM1 and DM2: In DM1, it is noted in face and jaw muscles, the drooping of the eyelids (ptosis), weakness of the neck muscles, hands and lower legs. In DM2, the weakness is more evident in proximal muscles, those closer to the trunk of the body: neck, shoulders, hip flexors and upper legs. Noted DM1 symptoms which are considered less severe or common for DM2 are problems with smooth muscle (including G.I. symptoms), hypersomnia (daytime sleepiness), muscle wasting, dysphagia and respiratory insufficiency. DM1 patients may experience a more diverse range of cognitive problems than DM2. Depending on what form they have and the degree of severity, DM1 cognitive problems may range from developmental delays, learning problems, language, speech, behaviour, apathy or hypersomnia. Cognitive manifestations for DM2 include problems with executive function (i.e. organization, concentration, word-finding etc) and hypersomnia. Conduction abnormalities are more common in DM1 than DM2, but all patients are advised to have an annual ECG. Insulin resistance is a significant risk factor in both forms of the disease for diabetes, cholesterol, heart, stroke, lipids, fatty liver, etc. Testing for insulin resistance must be at least 3 hours and include serial monitoring of the lipid profile and intermittent assessment of oral glucose tolerance testing as per the report from the 140th ENMC International Workshop: Myotonic Dystrophy DM2/PROMM and other myotonic dystrophies with guidelines on management (2006) Diabetes type 2 is suspected of being more common in DM2 than in DM1. Generally far fewer DM2 patients require assistive devices (canes, walkers, wheelchairs, scooters) than in DM1, though they experience increasing difficulties climbing stairs as the disease progresses, and falling or stumbling may sometimes be reported.
|
| Causes |
Mutations in the CNBP and DMPK genes cause myotonic dystrophy.
Myotonic dystrophy type 1 is caused by a mutation in the DMPK gene, while a mutation in the CNBP gene is responsible for the less common myotonic dystrophy type 2. The exact function of these genes is not known. The DMPK gene may play a role in communication within cells and appears to be important for the correct functioning of cells in the heart, brain, and muscles used for movement (skeletal muscles). The protein made by the CNBP gene is primarily found in the heart and in skeletal muscles, where it probably helps regulate the function of other genes.
Similar mutations in the DMPK and CNBP genes cause the two forms of myotonic dystrophy. In each case, a short segment of DNA is abnormally repeated many times, forming an unstable region in the gene. The mutated gene produces an altered version of messenger RNA, which is a molecular blueprint of the gene that is normally used for protein production. The abnormal messenger RNA forms clumps inside the cell that interfere with the production of many proteins. These changes prevent cells in muscles and other tissues from functioning normally, leading to the signs and symptoms of myotonic dystrophy. |
| Diagnosis |
The diagnosis of DM1 and DM2 can be difficult and may be delayed due to the large number of neuromuscular disorders, most of which are very rare. Neuromuscular disorders can cover more than 40 different diseases and additional forms of these bring the number of distinct disorders close to 100. As a result, patients with multiple symptoms that may be explained by a complex disorder such as DM1 or DM2 will generally be referred by their family doctor to a neuromuscular specialist for diagnosis. Depending on the presentation of symptoms, patients may be referred to a number of medical specialists including cardiologists, ophthalmologists, endocrinologists, rheumatologists. In addition, the clinical presentation varies considerably depending on the degree of severity or the presence of unusual phenotypes, so making diagnosis even more difficult. Some neuromuscular specialists focus primarily on many of the childhood onset neuromuscular diseases, while others may have research and clinical interests focused on specific diseases such as ALS and may be unaware of the potential relationship of specific symptoms to DM. It is common that the clinical presentation for both DM1 and DM2 patients does not conform to the perceptions of these diseases held by many neurologists. Clinicians who are less familiar with the myotonic dystrophies in their day to day practice may expect patients with both forms to present with the more severe classic symptoms of DM1. As a result, patients may remain undiagnosed or be misdiagnosed. Even though there is presently no cure for DM and management is currently symptom based, a precise diagnosis is still necessary because of multiple other problems that may develop over time. Even mildly affected DM1 & DM2 patients should be routinely monitored for potentially fatal complications (i.e. cardiac conduction issues, insulin resistance, cataracts). An accurate diagnosis is important to assist with appropriate medical monitoring and medical management of symptoms. In addition, genetic counseling should be made available to all patients because of the high risk of transmission. Potentially serious anesthetic risks are important to note, so the presence of this disorder should be brought to the attention of all medical providers.
|
| Treatment |
|
|
|
