Myotonic Dystrophy
Last updated 21st November 2017 by Tom Heaton
Myotonic dystrophy (Dystrophia myotonica) is a subgroup of muscular dystrophy, with a particular clinical picture.
As with many of the muscular dystrophies, the term encompasses a fairly heterogeneous group of clinical and genetic disorders but with some similar features.
There 2 main forms describes:
Type 1 (DM1) was previously known as Steinert disease
Type 2 (DM2) is more recently recognised as a milder form or type 1.
It is the most common form of muscular dystrophy of adult onset and in those of european ancestry.
The inheritance pattern is autosomal dominant.
As with many of the muscular dystrophies, the term encompasses a fairly heterogeneous group of clinical and genetic disorders but with some similar features.
There 2 main forms describes:
Type 1 (DM1) was previously known as Steinert disease
Type 2 (DM2) is more recently recognised as a milder form or type 1.
It is the most common form of muscular dystrophy of adult onset and in those of european ancestry.
The inheritance pattern is autosomal dominant.
This is a good video from the Osmosis team:
https://www.youtube.com/watch?v=6XOAYzfFHmE
https://www.youtube.com/watch?v=6XOAYzfFHmE
Pathophysiology
In DM1, there is a mutation in the dystrophia myotonica protein kinase (DMPK) gene on chromosome 19q.
This is recognised as an expansion of a single CTG trinucleotide, which can be repeated a large number of times.
This undergoes transcription (into RNA) but not translation (into protein).
This provides a fairly novel disease mechanism - that of RNA toxicity.
The anormal RNA has a negative impact on the normal processes of other protein machinery in the cell, resulting in the manifestations of the disease..
This includes the bridging integrator 1 gene (contributing to the weakness), the skeletal muscle chloride channel (myotonia), insulin receptor (insulin resistance) and cardiac troponin (cardiac disturbances)
This is recognised as an expansion of a single CTG trinucleotide, which can be repeated a large number of times.
This undergoes transcription (into RNA) but not translation (into protein).
This provides a fairly novel disease mechanism - that of RNA toxicity.
The anormal RNA has a negative impact on the normal processes of other protein machinery in the cell, resulting in the manifestations of the disease..
This includes the bridging integrator 1 gene (contributing to the weakness), the skeletal muscle chloride channel (myotonia), insulin receptor (insulin resistance) and cardiac troponin (cardiac disturbances)
Presentation
The ‘classic’ DM1 presentation is described, but there can be much variability.
The presentation is usually in late teens or early adult life.
The key features are:
Weakness
Weakness commonly involves the facial and distal limb muscles.
Initially, more proximal skeletal muscle weakness is less common, as is involvement of the limb girdles, respiratory, ‘bulbar’ or ocular muscles.
There is associated muscle wasting.
The weakness is gradually progressive, and may lead to involving more proximal muscles.
Muscle pain is a common feature, and not particularly linked to the myotonia.
Myotonia
This is slow relaxation following a normal contraction.
It is more prominent in the early stages, and universal in DM1.
It is most noticeable in the hands, face, jaw and tongue.
Cardiac abnormalities
DM1 is associated with a number of cardiac abnormalities which may contribute to early mortality:
The form of conduction disturbances is very varied.
Atrial fibrillation and flutter are common.
There can be prolongation of PR and QRS complexes.
Heart blocks may also be present.
A range of structural cardiac changes can occur.
There may be left ventricular hypertrophy or dilation.
Mitral valve prolapse occurs in about 20% of patients.
Respiratory Impairment
Specific respiratory involvement may occur too.
Some of this is related to weakness and myotonia of the respiratory and pharyngoesophageal muscles.
There may also be a centrally driven respiratory depression.
Bulbar palsy may result in impaired swallowing and aspiration.
Endocrine Abnormalities
Primary hypogonadism is a common problem in DM1.
Insulin resistance is also common, although frank diabetes less so.
Gastrointestinal
Smooth muscle involvement is a common part of DM1.
This can result in a range of GU upset (abdominal pain, variable bowel habits, pseudo obstruction).
There may be impaired gastric emptying.
Cognitive Impairment
Cognitive impairment can involve a wide variety of cognitive domains.
Earlier onset is often associated with worse impairment.
Other
There are a couple of other common characteristics of the condition:
The presentation is usually in late teens or early adult life.
The key features are:
- Weakness
- Myotonia
- Cardiac abnormalities
- Respiratory impairment
- Endocrine abnormalities
- GI disturbances
- Cognitive impairment
- Other - cataracts, frontal balding
Weakness
Weakness commonly involves the facial and distal limb muscles.
Initially, more proximal skeletal muscle weakness is less common, as is involvement of the limb girdles, respiratory, ‘bulbar’ or ocular muscles.
There is associated muscle wasting.
The weakness is gradually progressive, and may lead to involving more proximal muscles.
Muscle pain is a common feature, and not particularly linked to the myotonia.
Myotonia
This is slow relaxation following a normal contraction.
It is more prominent in the early stages, and universal in DM1.
It is most noticeable in the hands, face, jaw and tongue.
Cardiac abnormalities
DM1 is associated with a number of cardiac abnormalities which may contribute to early mortality:
- Cardiomyopathy
- Conduction disturbances - arrhythmias
- Mitral valve prolapse
The form of conduction disturbances is very varied.
Atrial fibrillation and flutter are common.
There can be prolongation of PR and QRS complexes.
Heart blocks may also be present.
A range of structural cardiac changes can occur.
There may be left ventricular hypertrophy or dilation.
Mitral valve prolapse occurs in about 20% of patients.
Respiratory Impairment
Specific respiratory involvement may occur too.
Some of this is related to weakness and myotonia of the respiratory and pharyngoesophageal muscles.
There may also be a centrally driven respiratory depression.
Bulbar palsy may result in impaired swallowing and aspiration.
Endocrine Abnormalities
Primary hypogonadism is a common problem in DM1.
Insulin resistance is also common, although frank diabetes less so.
Gastrointestinal
Smooth muscle involvement is a common part of DM1.
This can result in a range of GU upset (abdominal pain, variable bowel habits, pseudo obstruction).
There may be impaired gastric emptying.
Cognitive Impairment
Cognitive impairment can involve a wide variety of cognitive domains.
Earlier onset is often associated with worse impairment.
Other
There are a couple of other common characteristics of the condition:
- Cataracts - occur in almost all patients
- Frontal balding
Diagnosis
This can often be made clinically.
Confirmation can be done through genetic testing.
Electromyogram (EMG) studies are often not needed, but can help in challenging diagnostic cases.
Confirmation can be done through genetic testing.
Electromyogram (EMG) studies are often not needed, but can help in challenging diagnostic cases.
Anaesthetic Management
The combination of adverse features in many patients with myotonic dystrophy make the condition particularly high risk for anaesthesia.
Preoperative assessment
A careful history is essential, to understand the particular expression of the disease in the patient.
Particular areas that need exploring include: respiratory symptoms, bulbar dysfunction, cardiac dysfunction and endocrine dysfunction.
Recent investigations should be available to provide further information on some of these adverse features:
Perioperative
Some key concerns may guide the anaesthetic plan:
Regional anaesthesia provides several advantages to general anaesthesia in these patients and is generally advocated if feasible.
Intubation can often be achieved without the requirement for muscle relaxants e.g. remifentanil infusion, and may be preferable.
Unlike some patients with muscular dystrophy, patients with myotonic dystrophy are not thought to be at increased risk of malignant hyperpyrexia.
Postoperative
A critical care admission postoperatively is essential for anything but the most minor peripheral surgery.
Patients require close observation to ensure adequate recovery from the impact of the anaesthesia and surgery.
An analgesic regimen that avoids the use of opioids and other depressant analgesia agents is highly desirable.
Preoperative assessment
A careful history is essential, to understand the particular expression of the disease in the patient.
Particular areas that need exploring include: respiratory symptoms, bulbar dysfunction, cardiac dysfunction and endocrine dysfunction.
Recent investigations should be available to provide further information on some of these adverse features:
- ECG - to assess for conduction abnormalities
- Echocardiogram - to look for evidence of structural heart disease and provide assessment of function
- Spirometry - may provide information about nature of respiratory symptoms
- ABG - as above
Perioperative
Some key concerns may guide the anaesthetic plan:
- Depolarising neuromuscular blockade
- Upregulation of ACh receptors can produce increased sensitivity
- Prolonged muscular contraction can result
- This can cause significant potassium release and cardiac disturbance
- Non-depolarising neuromuscular blockade
- Safe to use but may be poorly effective
- Neostigmine for reversal can result in muscle contraction
- Drugs with predictable offset (atracurium, mivacurium) without the use of a reversal agent or rocuronium with sugammadex are options.
- Nerve stimulation can produce myotonia
- Myotonia
- Myotonia can be triggered by hypothermia (and shivering) and electrical stimulation and these factors should be avoided.
- Regional anaesthesia doesn’t block myotonia. Local anaesthetic directly into the muscle can help with spasm.
- Sedative sensitivity
- Patients can be very sensitive to even small doses of anaesthetic agents, from both a cardiovascular and respiratory perspective.
Regional anaesthesia provides several advantages to general anaesthesia in these patients and is generally advocated if feasible.
Intubation can often be achieved without the requirement for muscle relaxants e.g. remifentanil infusion, and may be preferable.
Unlike some patients with muscular dystrophy, patients with myotonic dystrophy are not thought to be at increased risk of malignant hyperpyrexia.
Postoperative
A critical care admission postoperatively is essential for anything but the most minor peripheral surgery.
Patients require close observation to ensure adequate recovery from the impact of the anaesthesia and surgery.
An analgesic regimen that avoids the use of opioids and other depressant analgesia agents is highly desirable.
Links & References
- Marsh, S. Pittard, A. Neuromuscular disorders and anaesthesia. Part 1: generic anaesthetic management. CEACCP. 2011. 11(4): 115-118. Available at: https://academic.oup.com/bjaed/article/11/4/115/267032
- Marsh, S. Pittard, A. Neuromuscular disorders and anaesthesia. Part 2: specific neuromuscular disorders. CEACCP. 2011. 11(4): 119-123. Available at: https://academic.oup.com/bjaed/article/11/4/119/266998
- Allman, K. Wilson, I (eds). Oxford handbook of anaesthesia (3rd ed). 2012. Oxford University Press
- Beers, M. et al (eds). The Merck Manual (18th ed). Mitral regurgitation. 2006. Merck Research Laboratories.
- Darras, B. Chad, D. Myotonic dystrophy: treatment and prognosis. 2017. UpToDate. Available at: https://www.uptodate.com/contents/myotonic-dystrophy-treatment-and-prognosis?source=see_link#H17
- Darras, B. Chad, D. Myotonic dystrophy: Etiology, clinical features and diagnosis. 2017. UpToDate. Available at: https://www.uptodate.com/contents/myotonic-dystrophy-etiology-clinical-features-and-diagnosis
