Bay Biosciences provides high quality, clinical grade, cryogenically preserved muscular dystrophy biopsy tissue samples with matched FFPE’s, K2EDTA plasma, sera (serum) and peripheral blood mononuclear cells (PBMC), bio-fluid samples from DM1 myotonic muscular dystrophy patients.
The K2EDTA plasma, sera (serum) and PBMC bio-fluid specimens are processed from myotonic muscular dystrophy DM1 patient’s peripheral whole-blood using customized collection and processing protocols.
Myotonic Dystrophy Overview
Myotonic dystrophy (DM) is an inherited multisystem condition that mainly causes progressive muscle loss, weakness and myotonia. It can also affect other parts of your body, including your heart, lungs and eyes. There’s no cure for DM, but certain treatments and therapies can help manage symptoms and improve quality of life.
DM is a form of muscular dystrophy that affects muscles and many other organs in the body. The word “myotonic” is the adjectival form of the word “myotonia,” defined as an inability to relax muscles at will.
The term “muscular dystrophy” means progressive muscle degeneration, with weakness and shrinkage of the muscle tissue.
Myotonic dystrophy often is abbreviated as “DM” in reference to its Greek name, dystrophia myotonica. Another name used occasionally for this disorder is Steinert disease, after the German doctor who originally described the disorder in 1909.
DM is a complex, inherited condition that mainly causes progressive muscle atrophy and weakness. Patients with the condition often have prolonged muscle contractions (myotonia) and can’t relax certain muscles after using them.
Myotonic dystrophy (DM) has a wide range of symptoms. It can affect several body systems, including the following:
- Cardiovascular system
- Central Nervous System
- Eyes
- Endocrine system
- Skeletal muscles and heart muscles
Types of Myotonic Dystrophy
Myotonic muscular dystrophy is divided into the following two types:
- DM1 or Type-1 DM, develops when a gene on chromosome 19 called DMPK contains an abnormally expanded section located close to the regulation region of another gene, SIX5.
- DM2 or Type-2 DM T, recognized in 1994 as a milder version of DM1, is caused by an abnormally expanded section in a gene on chromosome 3 called ZNF9.
The expanded sections of DNA in these two genes appear to have many complex effects on various cellular processes. In both DM1 and DM2, the repeat expansion is transcribed into RNA but remains untranslated in protein.
Muscular Dystrophy Vs. Myotonic Dystrophy
Muscular dystrophy refers to a group of more than 30 inherited (genetic) conditions that cause muscle weakness. These conditions are a type of myopathy, a disease of the skeletal muscles. Over time, the muscles shrink and become weaker.
This affects your ability to walk and perform daily activities. It can also affect your heart and lungs.
Myotonic dystrophy is one type of muscular dystrophy. It’s the most common form of muscular dystrophy that begins in adulthood. (But certain types of myotonic dystrophy begin in infancy or childhood.)
Who can be affected by Myotonic Dystrophy?
Myotonic dystrophy (DM) affects at least 1 in 8,000 people across the world, though the prevalence of it varies among different geographic and ethnic populations. DM is the most common muscular dystrophy in people of European ancestry.
In most populations, type 1 is more common than type 2.
Different forms of myotonic dystrophy begin at different ages:
- Classic myotonic dystrophy type 1: This form usually begins in your 20s, 30s or 40s.
- Mild myotonic dystrophy type 1: This form affects people 20 to 70 years old (typically after the age of 40).
- Congenital myotonic dystrophy type 1: This form affects infants (“congenital” means “present at birth”).
- Childhood myotonic dystrophy type 1: This form usually begins around the age of 10.
- Myotonic dystrophy type 2: This form typically begins in adulthood. The average age of onset is 48 years.
Signs and Symptoms of Myotonic Dystrophy
The main symptoms of myotonic dystrophy include the following, which get progressively worse over time:
- Muscle atrophy (wasting)
- Myotonia
- Muscle weakness
Myotonia is the inability to relax muscles at will. For example, it may be difficult for someone with DM to let go of a door handle after grasping it.
However, DM can affect many different parts of your body and cause a variety of other symptoms. The severity and rate at which these symptoms develop depend on the type of DM.
Symptoms of Classic Myotonic Dystrophy Type-1
Symptoms of classic myotonic dystrophy type-1 usually begins in adulthood. Myotonia is the main initial symptom. It’s often more obvious after rest and improves with muscle activity.
Other symptoms include:
- A thin, sharp face (myopathic face) due to wasting of facial muscles.
- Distal muscle weakness (the muscles farthest from the center of your body), which results in difficulty with fine motor tasks involving your hands and an impaired gait due to foot drop.
- Heart conduction abnormalities.
Symptoms of Congenital Myotonic Dystrophy Type-1
Signs of congenital myotonic dystrophy before birth include the following:
- Decrease in fetal movement in the uterus
- Polyhydramnios (too much amniotic fluid around the fetus during pregnancy)
- Clubfoot
- Ventriculomegaly (enlarged brain ventricles due to a buildup of cerebrospinal fluid)
Symptoms of congenital DM in children and adults include the following:
- A tented appearance of your upper lip that results from weak facial muscles
- Decreased muscle tone (hypotonia), rather than myotonia
- Intellectual disability.
- Slurred speech (dysarthria)
Causes of Myotonic Dystrophy
Myotonic dystrophy (DM) is inherited (passed from parent to biological child). Mutations (changes) in the DMPK gene cause myotonic dystrophy type-1, while mutations in the CNBP gene cause type- 2.
Type-1 myotonic dystrophy (DM1) and type-2 myotonic dystrophy (DM2) are both caused by abnormally expanded stretches of DNA. The expansions occur in two different genes but appear to have similar effects on various cells, particularly the cells of the voluntary and involuntary muscles, including the heart and nervous system.
DM provides an example of mechanism of disease called RNA toxicity, which results from the expanded repeats in the flawed gene transcripts.
Scientific evidence suggests that excess messenger RNA generated from the abnormal DNA repeats is toxic and interferes with the production of many proteins in cells, which, in turn, causes signs and symptoms in various organs in myotonic dystrophy.
DNA expansion in DMPK gene causes DM1
In DM1, the abnormal DNA expansion is in the DMPK (dystrophia myotonica protein kinase) gene on chromosome 19 q 13.3. The defect was identified in 1992 as the cause of DM1.
Type-1 DM (DM1), long known as Steinert disease, occurs when a gene on chromosome 19 called DMPK contains an abnormally expanded section located close to the regulation region of another gene, SIX5.
Type-2 DM (DM2), recognized in 1994 as a milder version of DM1, is caused by an abnormally expanded section in a gene on chromosome 3 called ZNF9. DM2 was originally called PROMM, for proximal myotonic myopathy, a term that has remained in use but is somewhat less common than the term DM2.
The expanded sections of DNA in these two genes appear to have many complex effects on various cellular processes. In both DM1 and DM2, the repeat expansion is transcribed into RNA but remains untranslated in protein.
Myotonic Dystrophy Inheritance
Both types of myotonic dystrophy are inherited in an autosomal dominant pattern. When a trait is autosomal dominant, only one parent needs to have an altered gene to pass it on. Half of the children of a biological parent with an autosomal trait will get that trait.
As myotonic dystrophy type 1 is passed from one generation to the next, the condition generally begins earlier and earlier in life, and signs and symptoms become more severe. This phenomenon is called anticipation.
Prevention of Myotonic Dystrophy
As myotonic dystrophy (DM) is an inherited condition, there’s nothing you can do to prevent it.
If you’re concerned about the risk of passing on DM or other genetic conditions before trying to have a biological child, talk to your healthcare provider about genetic counseling.
Diagnosis of Myotonic Dystrophy
To diagnose myotonic dystrophy a healthcare provider will perform a physical exam and ask following questions about the patients:
- Personal medical history.
- Family medical history, especially a history of DM.
- Symptoms.
Following medical tests can help confirm a myotonic dystrophy diagnosis:
Genetic testing can confirm a diagnosis of myotonic dystrophy (DM). The testing looks for mutations in the DMPK gene (in DM1) or the CNBP gene (in DM2).
If your healthcare provider is unsure if you may have DM or another condition, they may order one or more of the following tests before recommending genetic testing:
- Creatine Kinase Blood Test: Creatine kinase is an enzyme that mainly exists in your heart and skeletal muscle. The cells in your skeletal muscles or heart muscles release creatine kinase into your blood when they’re damaged. In people with mild myotonic dystrophy, it may be mildly elevated but is typically normal.
- Electromyogram (EMG): This test involves checking electrical activity of muscle fibers using a fine needle electrode that’s inserted into your muscles. Typically, people with myotonic dystrophy have excessive waxing and waning electrical activity in their muscles at rest.
- Muscle Biopsy: For a muscle biopsy, a provider will remove a small sample of tissue and cells from one of your muscles. They’ll then analyze it under a microscope to look for signs of DM.
If these tests confirm a diagnosis of DM, your provider will likely recommend more tests to check the functioning of certain organs DM can affect. These tests include:
- Electrocardiogram to check your heart function.
- Pulmonary (lung) fucntion testing to check for neuromuscular respiratory failure.
- Sleep study to check for obstructive sleep apnea and hypersonic (daytime sleepiness).
Treatment of Myotonic Dystrophy
There’s no cure for myotonic dystrophy (DM). The treatment mostly focuses on:
- Managing symptoms.
- Maximizing quality of life and independence.
DM can affect many different parts of your body. Depending on your symptoms, treatment may include:
- Medications that reduce sustained myotonia, including sodium channel blockers such as mexilentine, tricyclic antidepressants, benzodiazepines or calcium antagonists.
- A CPAP machine for sleep apnea.
- Neurostimulants such asmethylphenidate for excessive daytime sleepiness.
- Cataract surgery for cataracts that impair your vision.
- Treatment for diabetes, which may involve medications in pill form and/or insulin. People with DM are at an increased risk of diabetes from insulin resistance.
- Synthetic testosterone for the treatment of low testosterone (male hypogonadism). Men and people assigned male at birth with DM1 commonly have low testosterone and erectile dysfunction.
Physical and occupational therapy are a significant part of maximizing independence for patients with DM. It can help strengthen the muscles and help you learn new ways of performing daily tasks. Assistive devices, such as braces, canes or a wheelchair can also help with independence.
Speech-language pathology (SLP) can help with difficulty swallowing (dysphagia) and slurred speech (dysarthria).
Life Expectancy of Someone with Myotonic Dystrophy
The average life expectancy for myotonic dystrophy depends on the type.
The neonatal mortality rate (death that occurs within 28 days after birth) is around 18% for infants with congenital DM1. About 25% of people with congenital DM1 die before 18 months of age and 50% die before their mid-30s.
Patients with mild DM1 usually have normal lifespans. Lifespan is reduced compared to average in classic DM1.
Myotonic dystrophy (DM) can be fatal, though the age at which DM may cause death depends on the type. The leading cause of death in DM is neuromuscular-associated respiratory failure, followed by cardiovascular complications.
Prognosis of Myotonic Dystrophy
The prognosis (outlook) of myotonic dystrophy (DM) depends on the type and the age it begins. An earlier age of symptom onset is generally associated with poorer outcomes and reduced survival rates.
Up to 50% of patients with myotonic dystrophy type 1 need a wheelchair for mobility before death. Patients with myotonic dystrophy type 2 have milder symptoms and typically don’t need assistive devices for mobility.
Bay Biosciences is a global leader in providing researchers with high quality, clinical grade, fully characterized human tissue samples, bio-specimens, and human bio-fluid collections.
Samples available include cancer (tumor) tissue, cancer serum, cancer plasma, cancer, peripheral blood mononuclear cells (PBMC). and human tissue samples from most other therapeutic areas and diseases.
Bay Biosciences maintains and manages its own biorepository, the human tissue bank (biobank) consisting of thousands of diseased samples (specimens) and from normal healthy donors available in all formats and types.
Our biobank procures and stores fully consented, deidentified and institutional review boards (IRB) approved human tissue samples and matched controls.
All our human tissue collections, human specimens and human bio-fluids are provided with detailed, samples associated patient’s clinical data.
This critical patient’s clinical data includes information relating to their past and current disease, treatment history, lifestyle choices, biomarkers, and genetic information.
Patient’s data is extremely valuable for researchers and is used to help identify new effective treatments (drug discovery & development) in oncology, and other therapeutic areas and diseases.
Bay Biosciences banks wide variety of human tissue samples and biological samples, including cryogenically preserved at – 80°C.
Including fresh frozen tissue samples, tumor tissue samples, formalin-fixed paraffin-embedded (FFPE), tissue slides, with matching human bio-fluids, whole blood and blood-derived products such as serum, plasma and PBMC.
Bay Biosciences is a global leader in collecting and providing human tissue samples according to the specified requirements and customized, tailor-made collection protocols.
Please contact us anytime to discuss your special research projects and customized human tissue sample requirements.
Bay Biosciences provides human tissue samples (human specimens) from diseased and normal healthy donors which includes:
- Peripheral whole-blood
- Amniotic fluid
- Bronchoalveolar lavage fluid (BAL)
- Sputum
- Pleural effusion
- Cerebrospinal fluid (CSF)
- Serum (sera)
- Plasma
- Peripheral blood mononuclear cells (PBMC)
- Saliva
- Buffy coat
- Urine
- Stool samples
- Aqueous humor
- Vitreous humor
- Kidney stones (renal calculi)
- Other bodily fluids from most diseases including cancer.
We can also procure most human bio-specimens, special collections and requests for human samples that are difficult to find. All our human tissue samples are procured through IRB-approved clinical protocols and procedures.
In addition to the standard processing protocols, Bay Biosciences can also provide human plasma, serum, and PBMC bio-fluid samples using custom processing protocols; you buy donor-specific collections in higher volumes and specified sample aliquots from us.
Bay Biosciences also provides human samples from normal healthy donors; volunteers, for controls and clinical research, contact us Now.
- 日本のお客様は、ベイバイオサイエンスジャパンBay Biosciences Japanまたはhttp://baybiosciences-jp.com/contact/までご連絡ください。