Introduction

Myotonic dystrophy (DM) is a rare progressive genetic disorder characterised by muscular weakness beginning in adulthood.¹ DM affects 3.6 million people all over the world.

Myotonia is the flawed relaxation of skeletal muscles followed by voluntary contraction or electrical stimulation.³ For example, individuals with myotonic dystrophy may find it difficult to leave their hands after a handshake.

Types of myotonias

Myotonia can be categorised into two types, both affecting the electrical process that regulates muscle contraction:

• Dystrophic -  This type is a genetic condition causing progressive muscle atrophy and weakness. It is a common dystrophy³               
• Non-dystrophic -  This type is known to alter  membrane excitability and is rare²

Types of dystrophic myotonia

DM can be further classified into two types, including:

• Myotonic dystrophy type 1 (DM1) is also called Steinert’s disease. It is a classic form of disease. The DMPK gene on chromosome19 undergoes mutation¹
• DM2 is proximal myotonic dystrophy, a mild variety of DM1. It is caused by the gene ZNF9 on chromosome 3 which undergoes a mutation¹

Difference between myotonic dystrophy and muscular dystrophy

When both are related to muscles it is essential we understand the difference between the two. Muscular dystrophy is a group of many genetic diseases that have progressive weakness and degeneration of muscles while performing voluntary actions.  On the other hand, myotonic dystrophy is a type of muscular dystrophy. It is most commonly seen in adults and overall.

Myotonic dystrophy type 1 

DM1 affects skeletal as well as smooth muscles and is classified as mild, classic or congenital.⁷

Mild DM1  

Mild DM1 is characterised by cataracts and mild myotonia. Additionally, those with mild DM1 may have a normal life span. 

Classic DM1 

Common characteristics of classic DM1 in adults include:

• Muscle weakness and wasting
• Myotonia 
• Cataracts 
• Cardiac abnormalities
• Physical handicap in adults

A short life span is associated with classic DM1. 

Congenital DM1 

Symptoms of DM1 can manifest at birth, causing life-threatening complications. This is known as congenital DM1. Congenital DM1 is characterised by hypotonia, generalised muscle weakness at birth and respiratory insufficiency which can lead to an early death.¹

Diagnosis

Diagnosis of DM1 may include: 

• Annual electrocardiogram
• 24-hour Holter monitoring
• Blood sugar fasting
• HbA₁C test 
• Eye  examination

Myotonic dystrophy type 2

DM2  is rare and there is an absence of a congenital form of the disease.

Clinical manifestations of DM2 include:

• Presents in adulthood
• Early onset of cataracts
• Grip myotonias
• Thigh muscle stiffness
• Muscle pain
• Weakness (in hip flexors, thigh muscles stiffness or long flexors of fingers)

How does myotonic dystrophy develop?

The genetic code allows the expression of the character associated with it. DM1 occurs due to a repeat sequence of three DNA nucleotides CTG (cytosine-thymine-guanine). DM2 occurs by a repeat sequence of four proteins CCTG (cytosine-cytosine-thymine-guanine). These repeated sequences produce abnormal proteins that disrupt normal cell functions.

Risk factors of myotonia

Factors that could increase the risk of developing myotonia include:

•    Cold temperature
•    Fasting/irregular meals
•    High or low potassium in food
•    Rest after exercise or warm-up
•    Stress
•    Disturbed sleep

Effects of myotonic dystrophy

Myotonic dystrophy can cause^{1, 4}

• Cardiac conduction defects,
• Balding
• Early cataracts 
• Cognitive impairment
• Thyroid dysfunctions
• Insulin resistance
• Infertility
• Excessive daytime sleepiness

Diabetes

Glucose is the fuel that our body needs to perform activities. Glucose provides energy to the cells to function.

Types of diabetes

• Type 1 diabetes is the autoimmune destruction of beta cells of the pancreas, leading to insulin deficiency. Altered lipid metabolism, hyperglycemia-mediated oxidative stress, and cell dysfunctions are also associated with it
• Type 2 diabetes is a metabolic disorder that occurs due to improper lifestyle
• Gestational diabetes occurs during pregnancy

 How diabetes occurs

 Type 1 diabetes occurs due to hyperglycemia as a result of insulin deficiency in the plasma.⁵

 Type 2 diabetes occurs due to:⁵

• Insulin receptor impairment
• Pancreatic exocrine disorder
• Genetic disorders
• Endocrine disorders
• Lifestyle

More glucose in the plasma causes the secretion of more insulin in the blood. This increased insulin secretion to balance hyperglycemia results in chronic symptoms such as: 

• Cardiovascular diseases
• Neuropathy
• Nephropathy
• Retinopathy

These chronic symptoms may lead to a heart attack or stroke.

Manifestations of diabetes

 Acute symptoms of diabetes include:

• Increased thirst
• Increased urination
• Increased hunger
• Unexplained weight loss

Myotonic dystrophy and endocrinopathies

About 10% of patients with myotonic dystrophy suffer from diabetes mellitus characterised by severe insulin resistance. Insulin, a hormone, controls the amount of sugar in the blood. Insulin resistance makes the body cells unresponsive to insulin. Glucose thus cannot enter the cells and builds up in the blood. This causes type 2 diabetes. ⁶

These patients may even have infertility issues. 

DM1 can affect the endocrine glands. These patients develop endocrinopathies with increasing age.  

Insulin resistance and myotonic dystrophy type 1 

Insulin resistance

In DM type 1 the body tissues do not respond to insulin that lowers the blood sugar level. This is known as insulin resistance. ⁸

Decreased muscle insulin sensitivity

Insulin sensitivity is reduced to 70% in muscles in DM type1 as compared to normal individuals. This means that the muscles absorb less glucose from the blood even when insulin is present.

Insulin sensitisers

Insulin sensitisers are effective in treating diabetes mellitus in patients with DM1. People suffering from DM1 also have insulin resistance due to the insulin receptors in the muscles. Medications that help in managing insulin resistance also help in managing DM1.

Diagnosis

DM can be  diagnosed by: 

• Physical examination - By checking for muscle tone and muscle wasting, which presents as reduced muscle mass, reduced muscle strength and inability to perform physical activity⁹
• Genetic diagnosis - A genetic evaluation of genes reveals DM1. Individuals with 35 to 49 repeats of nucleotide CTG in genes do not show any symptoms but can transfer more repeats to their offspring. The greater the number of repeats of CTG nucleotide earlier is the onset. It has been found that repeats above 50 have mutant genes and exhibit symptoms⁹
• The serum creatinine test Is elevated in these patients¹
• Hepatobiliary functions - Hepatobiliary enzymes, alkaline phosphatase and GGT are elevated¹
• Weakness - Several scales like the muscular impairment rating scale help to quantify weakness on a scale of 1 to 5⁹

Treatment

Myotonic dystrophy of any type has no cure. Treatment is restricted to managing symptoms and leading an independent quality life, for example:

• Using assistive devices like a wheelchair if required and ankle-foot appliances for  support
• NSAIDs (non-steroidal anti-inflammatory drugs) are given to relieve pain
• Cardiac consultation
• Cataract surgery for improving vision
• Hormone replacement for endocrinopathies. Treatment for diabetes and hypogonadism
• Neurostimulators for excessive daytime sleep
• Physical therapy is suggested for muscle strengthening

FAQs

How will myotonic dystrophy be treated in future?

Treatment of myotonic dystrophy currently is limited to assistive therapy but in the future CRISPR gene editing technology may prove to be helpful.

What is the prognosis of myotonic dystrophy? 

It depends upon the type of dystrophy one has. People with DM1 may need a wheelchair but people with DM2 have mild symptoms and may never need assistive devices. 

How common is myotonic dystrophy?

1 in 8000 people develop myotonic dystrophy. DM1 is more common than DM2.

How does myotonic dystrophy progress?

Both types have slow progress but DM1 has poor outcomes due to: 

• Diabetes
• Issues with blood pressure
• Respiratory problems
• Irregular heartbeats

Summary

Myotonic dystrophy (DM) is a genetic disorder. It is characterised by progressive muscle weakness. It exists in two main forms: type 1 and type 2. It is an autosomal dominant condition which means that people need to inherit one gene to present the symptoms.

DM type 1 is a common occurrence while DM type 2 is rare and is a mild form of type 1. It presents itself as muscle weakness, early cataract development, and endocrinopathies. People who suffer from DM also suffer from diabetes. It is challenging to diagnose, treat and manage DM because of its diverse manifestations. Medical advancements like CRISPR gene editing may help to improve the quality of life.