Steinert Syndrome

Author: Beatrice Silano
Date: 19/03/2013



Myotonic dystrophy (dystrophia myotonica, DM) is the most frequently inherited neuromuscular disease of adult life. Classical DM, also called Steinert disease for the German Doctor who first described this disease in 1909 as a dominantly transmitted muscular dystrophy, has been identified as an autosomal dominant disorder.

Best practice guidelines and recommendations on the molecular diagnosis of myotonic dystrophy types 1 and 2, 2012

WikipediaSteinert Syndrome
The Diseases DatabaseDM
MedlinePlusMyotonic dystrophy
OMIM single geneDM1


A decrease in the CTG repeat size during transmission from parents to child can also occur in about 6.4% of transmissions, most frequently during paternal transmission(10%). Myotonic dystrophy transmission: Type 1 Myotonic Dystrophy is dominant form of the disease that do not involve the sexual chromosome pairs. The anomaly is located on chromosome 19 for Type 1 Myotonic Dystrophy. This means that both girls and boys will be affected with the same frequency and that the risk of transmission of the disease will be one out of two for each child regardless of the sex. The incidence of DM1 is estimated to be 1 in 8000 births and its worldwide prevalence ranges from 2.1 to 14.3/100 000 inhabitants.


Based on the age of onset and on its clinical features, DM1 can be divided into three forms: congenital, classical, and minimal, which may occur in the same kindred. DM is a multisystem disease with major cardiac involvement. Core features of myotonic dystrophy are myotonia, muscle weakness, cataract, and cardiac conduction abnormalities. However, the localization of DMPK in the heart muscle at the level of intercalated discs, combined with the observation that DMPK reduction, in animal models, compromises the conduction at both the level of the atrioventricular node and the His-Purkinje system, suggest the impairment of intercellular impulse propagation as a possible mechanism of disease.

Myotonic dystrophy and the heart, 2002


The diagnosis is based on several criteria. First is the hereditary factor, when there are many cases present in the family. Second is the clinical factor, when in the subjects occur characteristic signs of the disease. When these two factors are present the diagnosis is easy. Sometimes the diagnosis is more complex because certain subjects have few signs of the disease while others have no signs at all.
Since 1992, when in doubt, the diagnosis for Myotonic Dystrophy is based on genetic analysis. This is done by a simple blood test that enables a diagnosis in almost 100% of cases. It consists in isolating the blood DNA that contains the genetic information and to measure the number of repetitions. Within the normal population, the number of repetitions is always inferior to 40, while in diseased subjects the number of repetitions can be as high as 4000 to 5000.
Beyond the diagnosis of the disease, genetic testing can give an idea of the extent of the disease, especially for the DM1 form. In general, the higher the number of repetitions, the worse the disease will be. There are of course numerous cases that do not follow this rule and thus do not make this a reliable tool for prognosis.


The genetic anomaly responsible for Type 1 Myotonic Dystrophy was identified in 1992. It is located on chromosome 19, a chromosome that is not implicated in the determination of the sex of the individual. This gene was identified as the gene for myotonin-protein kinase. This name comes from the fact that the gene carries the information to produce an enzyme which is part of the protein kinase family. The genetic basis of DM1 is known to include mutational expansion of a repetitive trinucleotide sequence (CTG) in the 3'-untranslated region of the DMPK (Dystrophia Myotonica Protein Kinase) gene on chromosome 19q13.3. The process leading from the abnormal expansion of CTG repeats in a non-coding region of DMPK gene to the cellular dysfunction is still incompletely understood.

Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9, 2001

Best practice guidelines and recommendations on the molecular diagnosis of myotonic dystrophy types 1 and 2, 2012


Cardiac involvement, that often precedes the skeletal muscle one, occurs in 80% of DM1 patients and represents the second most common cause of death, after respiratory causes. Endomyocardial biopsies performed on patients with DM1 have shown specific changes, such as perivascular interstitial fibrosis, fatty infiltration, hypertrophy of myocardiocites, and focal myocarditis.
Cardiac mortality usually occurs because of progressive left ventricular dysfunction, ischaemic heart disease, pulmonary embolism, or as a result of unexpected sudden death (SD)
Increased temporal dispersion of myocardial repolarization in myotonic dystrophy type 1: beyond the cardiac conduction system.
Myotonic dystrophy and cardiac involvement: key points

  • Cardiac involvement is mainly represented by conduction abnormalities at ECG
  • Conduction abnormalities are progressive, but the rate of progression is not clear
  • Ventricular arrhythmias are common
  • The unusual bundle branch re-entry ventricular tachycardia should be actively sought as radiofrequency ablation may be curative

• Sudden death represents 2–30% of fatalities in patients with DM1. Possible mechanisms are ventricular asystole, degeneration of ventricular tachycardia, ventricular fibrillation or electromechanical dissociation. The respective prevalence of these mechanisms is unknown
• Over myocardial dysfunction is rare; however, impairment of ventricular systolic and diastolic functions may be part of the cardiac scenario.
A careful cardiac evaluation including basal ECG, 24 hour Holter monitoring, echocardiogram, and signal averaged ECG should be routinely performed in all patients presenting with DM1. A history of fainting, palpitation, shortness of breath, lipothymia, and syncope should be carefully searched by interviewing not only the patient but also his or her relatives. Recent findings, however, suggest that a prolongation of HV interval beyond may warrant a prophylactic pacemaker implant even in the absence of symptoms.

Increased temporal dispersion of myocardial repolarization in myotonic dystrophy type 1: beyond the cardiac conduction system, 2012

Myotonic dystrophy and the heart, 2002

The heart and cardiac pacing in Steinert disease, 2012


On the disease treatment front, one study conducted in the USA concerning the administration of a growth hormone (IGF-1) did not show efficacy of this treatment of the disease manifestations, especially on muscle strength. Numerous presentations reported on the use of small molecules, called antisense oligonucleotides, able to neutralize the effects of the genetic anomaly. Intramuscular injections of these small molecules were able to improve the myotonia (what the patients describe as having locked hands) in a mouse model showing the signs of the disease. There is no evidence however, that this type of treatment could restore muscle strength or improve the other manifestations of this disorder. The advantage of these small molecules is their capacity for intravenous delivery, which could make them appealing to treat the numerous other disease manifestations. The main difficulty however, is their weak penetration into tissues, which limits their usefulness at the present. Even though these molecules bring some hope for the treatment of myotonic dystrophy, there are many obstacles to overcome before we can test them in humans. Another study demonstrated the efficacy of pentamidine, an antibiotic used to treat certain pneumonias, on the treatment of myotonia. There is no evidence however, of the effectiveness of this molecule to treat muscle weakness.
Treatment of myotonia by mexiletine: a study performed at the university of Rochester shows that mexiletine at dosages of 150 and 200 mg 3 times per day is effective, safe, and well-tolerated as an antimyotonia treatment in DM1.

Targeting nuclear RNA for in vivo correction of myotonic dystrophy, 2012

Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type1, 2010

Myotonic dystrophy and the heart, 2002

Beatrice Silano

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