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Dystrophies: myotonic
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(DM1 or Steinert disease, DM2 or Ricker syndrome or PROMM for Proximal Myotonic Myopathy)
Association of a muscular dystrophy, with myotonia and anomalies of other organs: eye (cataract), centrous nervous system, heart (conduction disorders, cardiomyopathy), lungs, digestive tract (dysphagia, constipation), endocrine system (diabetes with insulin resistance, hypogonadism). CK level are elevated. Myotonia is characterized by a delay or a difficulty to relax a muscle after its contraction whether spontaneous (handshake, forced closure of the eyelids) or induced (response to percussion). There is also a typical EMG trace. The myotonia present in the myotonic dystrophies can be subtle and improves with exercise ("warm up" phenomenon).
Inheritance is autosomal dominant with variable penetrance.
There are two types:
- type 1: corresponds to the classical description of Steinert
- type 2: described more recently (1992).
The incidence of both types is approximately 13/10,000. The prevalence of type 1 varies from 2.1 to 14.3/100,000, but is much higher in the region of Saguenay-Lac-Saint-Jean in Quebec (158/100.000)
Both types are considered to be diseases of the transcription of the messenger RNA. They are due to mutations in different genes but a part of the pathophysiology is common, which explains the similarity of some signs and symptoms. Both types seem to be associated with an increased risk of cancer partly linked to the number of repetitions of the CTG or CCTG polynucleotid: a regular and earlier screening than in the general population is thus recommended.
* Steinert disease :
The disease starts earlier and becomes more severe from generation to generation: this is called the amplification phenomenon.
The cause is the repeat amplification of the CTG trinucleotide in the noncoding region 3'of the gene that encodes for the DMPK protein (19q13.2-q13.3). The pathological amplification of CTG repetition (> 50) causes the nuclear sequestration of abnormal mRNA that transcribes DMPK. This accumulation disrupts synthesis and function of other genes such as the CLCN1 gene (Cl- channel), the insulin receptor, etc... It is therefore a secondary chanellopathy.
There are:
- congenital form (repetitions of CTG > 1500): major hypotonia with breathing problems, feeding difficulties, pulmonary aspirations. Typical facial appearance with a tent-shaped mouth. Significant mortality. The survivors have a gradual improvement of the hypotonia but have important mental retardation. Gradual emergence of the characteristics of the adult form.
- early infantile form: problems with learning and speech difficulties
- early adult form: hypotrophy of the masticatory muscles, poorly expressive facies, cataract, myotonia... Dilated cardiomyopathy with heart failure is of late onset but may be the first sign of the disease in forms with subtle muscle symptoms.
Cardiac involvement is constant, even in infants: conduction anomalies (block branch, AVB, ventricular tachyarrhythmias), sometimes mitral valve prolapse. A dilated cardiomyopathy can be observed. In the young adult with conduction problems (PR > 200msec or QRS > 100 msec), prophylactic placement of a pacemaker or internal cardiac defibrillator seems to improve survival and strongly reduces the risk of sudden death from cardiac causes.
The decrease in the response to hypercarbia (sleep apnea) and the increased sensitivity to the respiratory effects of the anesthetic agents (barbiturates, propofol, morphine, benzodiazepines) can cause slow awakening, post-anesthesia apneas, respiratory infectious complications or even require prolonged mechanical ventilation.
The gastrointestinal tract is affected, with dysphagia, decrease in gastric emptying time and a tendency to paralytic ileus. It is therefore prudent to place a gastric tube even for short duration intervention.
The presence of several pilomatricomas (see this term) should be a triggering factor to screen for a type I myotonic dystrophy.
Experimental treatment: Tideglusib (inhibitor of the glycogen synthase kinase 3).
* Type 2 form (DM2), [MIM 602 668, 116 955]
The ZNF9 gene (zinc finger protein 9) (3q21) is involved, and the noncoding repetition of the GTCC quadrinucleotide is the cause of the disease.
Clinical signs appear later (around the age of 8 to 50 years) and are similar to those of the type 1 but the muscle involvement is proximal with less myotonia and more cramps and myalgias. Sometimes diagnosed as fibromyalgia. There is no congenital form. Cardiac involvement is more discreet (left ventricular dysfunction) but cases of cardiomyopathy requiring heart transplantation have been described ; involvement of the coronary arteries is common. The risk of cataract is present. There is no increased sensitivity to anesthetic agents as in type 1.
Comparative table :
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Type 1 onset at adulthood |
Type 2 |
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Genetic gene locus mutation |
DMPK 19q13 expansion of CTG |
ZNF9 3q21 expansion of CCTG |
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onset |
neonatal, childhood
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adulthood |
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Facies frontal baldness, alopecia facial muscles atrophy cataract |
very frequent +++ posterior, subcapsular |
rare + posterior, subcapsular |
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SNC mental retardation cognitive dysfunction behavior problems visual/spatial deficits hypersomnia |
congenital form +++ ++ ++ ++ |
- rare rare rare + |
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Endocrine problems diabetes mellitus hypogonadism dysthyroidy |
+ ++ + |
+ + + |
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Digestive problems dysphagia constipation cholelithiasis high γGT |
severe ++ ++ + |
mild ++ + ++ |
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Cardiac problems Troubles of conduction AV or IV cardiomyopathy sudden death |
brady- or tachyarrhythmias dilated major risk |
may be present dilated less important risk ? |
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Muscular system weakness localisation myotonia myalgias high CK level |
mild to severe distal > proximal present rare ++ |
light to moderate proximal > distal moderate or absent very frequent ++ |
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sensitivity to general anesthetic agents |
+++ |
normal |
Anesthetic implications:
(1) the decrease in sensitivity to CO2 and the risk of central and obstructive apnea justify a prolonged stay in the recovery room monitoring or elective admission in the intensive care unit
(2) the risk of perioperative complications (particularly respiratory) is mainly related to the importance of muscular disability, the use of per or postoperative opiates or morphine and the use of a muscle relaxant without antagonization at the end of the procedure.
(3) the combination of remimazolam and remifentanil has been used successfully
√ hypnotic agents (propofol, thiopental, ketamine) and benzodiazepines (midazolam): an increased sensitivity to their hypnotic and respiratory effects has been described in many patients and seems unpredictable: it is therefore recommended to start with low doses and titrate subsequent doses according to the patient's response.
√ etomidate: unproblematic use
√ opiates: use the lowest possible doses; interest in remifentanil
√ alpha2 agonists: start with low doses and titrate subsequent doses according to patient’s response.
√ No succinylcholine, as there is a risk of producing a myotonic reaction (a few cases described). No cases of hyperkalemia have been described. Rocuronium appears to have a shortened onset of action and a prolonged duration of action.
√ monitoring curarization: acceleromyography seems to underestimate the depth of curarization: EMG-based monitoring is preferable. The use of neostigmine could theoretically lead to contracture, but no cases have been described. Sugammadex has been used without problem to antagonize rocuronium and vecuronium. Short-acting curares have been used without problems.
√ halogenated agents have been used without problems: no cases of anesthesia-induced rhabdomyolysis have been described.
√ locoregional anesthesia is very useful for avoiding general anesthesia or reducing its dose. In case of peripheral block, use ultrasound rather than neurostimulation.
References :
- Parness J, Bandschapp O, Girard T.
The myotonias and susceptibility to malignant hyperthermia.
Anesth Analg 2009, 109: 1054-64.
Updated: January 2024