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Myotonic Dystrophy Type 1

Synonym: Steinert's Disease
, MD
Seattle VA Medical Center
Departments of Neurology and Medicine
University of Washington
Seattle, Washington

Initial Posting: ; Last Revision: October 22, 2015.

Summary

Clinical characteristics.

Myotonic dystrophy type 1 (DM1) is a multisystem disorder that affects skeletal and smooth muscle as well as the eye, heart, endocrine system, and central nervous system. The clinical findings, which span a continuum from mild to severe, have been categorized into three somewhat overlapping phenotypes: mild, classic, and congenital.

  • Mild DM1 is characterized by cataract and mild myotonia (sustained muscle contraction); life span is normal.
  • Classic DM1 is characterized by muscle weakness and wasting, myotonia, cataract, and often cardiac conduction abnormalities; adults may become physically disabled and may have a shortened life span.
  • Congenital DM1 is characterized by hypotonia and severe generalized weakness at birth, often with respiratory insufficiency and early death; intellectual disability is common.

Diagnosis/testing.

DM1 is caused by expansion of a CTG trinucleotide repeat in the non-coding region of DMPK. The diagnosis of DM1 is suspected in individuals with characteristic muscle weakness and is confirmed by molecular genetic testing of DMPK. CTG repeat length exceeding 34 repeats is abnormal. Molecular genetic testing detects pathogenic variants in nearly 100% of affected individuals.

Management.

Treatment of manifestations: Use of ankle-foot orthoses, wheelchairs, or other assistive devices; treatment of hypothyroidism; management of pain; consultation with a cardiologist for symptoms or ECG evidence of arrhythmia; removal of cataracts if vision is impaired; hormone replacement therapy for males with hypogonadism; surgical excision of pilomatrixoma.

Surveillance: Annual ECG or 24-hour Holter monitoring; annual measurement of fasting serum glucose concentration and glycosylated hemoglobin concentration; eye examination every two years; attention to nutritional status.

Agents/circumstances to avoid: Cholesterol-lowering medications (i.e., statins), which can cause muscle pain and weakness; the anesthetic agent vecuronium.

Evaluation of relatives at risk: Molecular genetic testing for early diagnosis of relatives at risk to allow treatment of cardiac manifestations, diabetes mellitus, and cataracts.

Genetic counseling.

DM1 is inherited in an autosomal dominant manner. Offspring of an affected individual have a 50% chance of inheriting the expanded allele. Pathogenic alleles may expand in length during gametogenesis, resulting in the transmission of longer trinucleotide repeat alleles that may be associated with earlier onset and more severe disease than that observed in the parent. Prenatal testing is possible for pregnancies at increased risk when the diagnosis of DM1 has been confirmed by molecular genetic testing in an affected family member.

Diagnosis

Suggestive Findings

Myotonic dystrophy type 1 (DM1) should be suspected in adults with the following:

  • Muscle weakness, especially of the distal leg, hand, neck, and face
  • Myotonia (sustained muscle contraction), which often manifests as the inability to quickly release a hand grip (grip myotonia) and which can be demonstrated by tapping a muscle (e.g., the thenar muscles) with a reflex hammer (percussion myotonia)
  • Posterior subcapsular cataracts detectable as red and green iridescent opacities on slit lamp examination

DM1 should be suspected in neonates with some combination of the following:

  • Hypotonia
  • Facial muscle weakness
  • Generalized weakness
  • Positional malformations including club foot
  • Respiratory insufficiency

Testing

Electromyography (EMG). A needle electrode placed in the muscle of an affected adult records myotonic discharges and myopathic-appearing motor units, predominantly in distal muscles. Electrical myotonic discharges are not usually seen during infancy, but fast runs of single-fiber discharges approaching the pattern of myotonic discharges are suggestive.

Serum CK concentration. Serum CK concentration may be mildly elevated in individuals with DM1 with weakness, but is normal in asymptomatic individuals.

Muscle biopsy. Pathologic features observed on muscle biopsy include rows of internal nuclei (having a box car appearance), ring fibers, sarcoplasmic masses, type I fiber predominance and atrophy, fibrosis and fatty infiltration, and a greatly increased number of intrafusal muscle fibers [Thornton 2014, Turner & Hilton-Jones 2014].

Note: Non-molecular testing that has been used in the past to establish the diagnosis of DM1 currently has little role in diagnosis and is primarily used if molecular testing of DMPK does not identify the CTG repeat expansion and other myopathies are being considered.

Establishing the Diagnosis

The diagnosis of DM1 is established in a proband with identification of a heterozygous pathogenic variant in DMPK by molecular genetic testing (see Table 1).

Allele sizes. Reference ranges for allele sizes were established by the Second International Myotonic Dystrophy Consortium (IDMC) in 1999 [International Myotonic Dystrophy Consortium 2000, Moxley & Meola 2008] See Prior [2009] and Kamsteeg et al [2012] for technical standards and guidelines for testing.

  • Normal alleles. 5-34 CTG repeats
  • Mutable normal (premutation) alleles. 35-49 CTG repeats. Individuals with CTG expansions in the premutation range have not been reported to have symptoms, but their children are at increased risk of inheriting a larger repeat size and thus having symptoms [Martorell et al 2001].
  • Full penetrance alleles. >50 CTG repeats. Full penetrance alleles are associated with disease manifestations.

See Published Guidelines/Consensus Statements.

Molecular testing approaches can include targeted analysis and use of a multi-gene panel.

  • Targeted analysis for an increased number (i.e., an expansion) of the CTG trinucleotide repeat in DMPK .
  • A multi-gene panel that includes DMPK and other genes of interest (see Differential Diagnosis) may also be considered. Note: The genes included and sensitivity of multi-gene panels vary by laboratory and over time.

Table 1.

Summary of Molecular Genetic Testing Used in Myotonic Dystrophy Type 1

Gene 1Test MethodProportion of Probands with a Pathogenic Variant 2 Detectable by This Method
DMPKTargeted analysis for pathogenic variants 3100%
1.
2.

See Molecular Genetics for information on allelic variants detected in this gene.

3.

Testing to quantitate the number of DMPK CTG trinucleotide repeats is performed by PCR analysis, which reliably detects expanded alleles with about 100-150 CTG repeats. Detection of larger CTG expansions requires Southern blot analysis.

Clinical Characteristics

Clinical Description

Clinical findings in myotonic dystrophy type 1 (DM1) span a continuum from mild to severe. Udd & Krahe [2012], Thornton [2014], and Turner & Hilton-Jones [2014] provide an excellent overview of all aspects of DM1. The clinical findings have been categorized into three somewhat overlapping phenotypes (mild, classic, and congenital) that generally correlate with CTG repeat size (Table 2). The CTG repeat ranges for the phenotypes in Table 2 have considerable overlap and caution must be used in predicting disease severity on the basis of CTG repeat size [Gharehbaghi-Schnell et al 1998, International Myotonic Dystrophy Consortium 2000, Harper 2001, Moxley & Meola 2008].

Table 2.

Correlation of Phenotype and CTG Repeat Length in Myotonic Dystrophy Type 1

PhenotypeClinical SignsCTG Repeat Size 1, 2Age of OnsetAverage Age of Death
Mutable normal (premutation)None35-49NANA
MildCataracts
Mild myotonia
50-~15020-70 yrs60 yrs to normal life span
ClassicWeakness
Myotonia
Cataracts
Balding
Cardiac arrhythmia
Others
~100-~100010-30 yrs48-55 yrs
CongenitalInfantile hypotonia
Respiratory deficits
Intellectual disability
Classic signs present in adults
>1000 3Birth to 10 yrs45 yrs 4

NA = not applicable

1.

CTG repeat sizes are known to overlap between phenotypes.

2.

Normal CTG repeat size is 5-34.

3.

Redman et al [1993] reported a few individuals with congenital DM1 with repeats between 730 and 1000.

4.

Does not include neonatal deaths

Mild DM1

Individuals with mild DM1 may have only cataract, mild myotonia, or diabetes mellitus. They may have fully active lives and a normal or minimally shortened life span [Arsenault et al 2006].

Classic DM1

Within this range of CTG repeat size, only a rough correlation with severity of symptoms exists. Individuals with CTG repeat sizes in the 100-to-1000 range usually develop classic DM1 with muscle weakness and wasting, myotonia, cataracts, and often cardiac conduction abnormalities.

While the age of onset for classic DM1 is typically in the 20s and 30s (and less commonly after age 40 years), classic DM1 may be evident in childhood, when subtle signs such as myotonia and typical facial features including ptosis, weak eye lid closure, weak smile, and thin face are observed.

Muscle. In individuals with classic DM1, the predominant symptom is distal muscle weakness, leading to foot drop/gait disturbance and difficulty performing tasks that require fine manual dexterity. The typical facial appearance is mainly caused by weakness of the facial and levator palpebrae muscles. Myotonia may interfere with daily activities such as using tools, household equipment, or doorknobs. Handgrip myotonia and strength may improve with repeated contractions (the so-called warm-up phenomenon) [Logigian et al 2005]. The warm-up phenomenon can also improve dysarthric speech [de Swart et al 2004]. Muscle weakness is progressive but slow, and correlates with disease duration and CTG repeat expansion size [Bouchard et al 2015]

Fatigue is a common finding [Kalkman et al 2005].

Musculoskeletal pain is fairly common, especially in the lower limbs.

Cardiac. Cardiac conduction defects of varying degrees of severity are common. In one series, 90% of individuals had conduction defects. These defects are a significant cause of early mortality in individuals with DM1, sometimes associated with sudden death. Cardiac pacemaker is sometimes indicated. Less commonly, dilated cardiomyopathy may occur [Bassez et al 2004, Chebel et al 2005, Dello Russo et al 2006, Sovari et al 2007, Breton & Mathieu 2009, Mörner et al 2010, Petri et al 2012, Turkbey et al 2012, Lund et al 2014, Benhayon et al 2015, Lau et al 2015].

GI. Smooth muscle involvement may produce dysphagia, constipation, intestinal pseudo-obstruction, or diarrhea [Rönnblom et al 1996, Bellini et al 2006, Glaser et al 2015]. Oropharyngeal dysphagia and swallowing problems have been studied by Ercolin et al [2013].

Gallstones occur as a result of increased tone of the gall bladder sphincter.

Liver function tests (e.g., transaminases) are often elevated for unclear reasons [Heatwole et al 2006].

Cognition and CNS changes. Minor intellectual deficits are present in some individuals, but in others intelligence may be incorrectly assumed to be reduced because of the dull facial expression. Age-related cognitive decline has been reported in some adults [Modoni et al 2004, Gaul et al 2006, Sansone et al 2007, Modoni et al 2008]. Overall full-scale IQ tends to be lower in individuals with both mild and classic DM1 [Jean et al 2014].

Frontal-parietal lobe deficits have been documented on formal testing [Sistiaga et al 2010].

Avoidant, obsessive-compulsive, and passive-aggressive personality features have been reported [Delaporte 1998, Winblad et al 2005]. Peric et al [2014] reported pathologic personality traits in 58% of 62 patients tested, the two most common being dependent and/or paranoid personality.

In one study of 200 patients with DM1, personality traits and psychological symptoms were usually in the normal range, but 27% were at high risk of developing a psychiatric disorder [Bertrand et al 2015].

Anxiety and depression are often seen and general quality of life can be seriously impaired [Antonini et al 2006].

Hypersomnia and sleep apnea are other well-recognized manifestations that appear later [Rubinsztein et al 1998, Laberge et al 2009]. Excessive daytime sleepiness is often caused by a central dysfunction of sleep regulation, but all types of sleep disorders have been reported [Dauvilliers & Laberge 2012]. Fifty percent of 40 individuals with DM1 had obstructive sleep apnea [Pincherle et al 2012].

Brain MRI may demonstrate mild cortical atrophy and white matter abnormalities. The white matter changes can be diffuse and extensive [Romeo et al 2010, Minnerop et al 2011, Wozniak et al 2013, Caso et al 2014]. Proton magnetic resonance spectroscopy shows probable glutamatergic neuronal degeneration in frontal cortex and white matter [Takado et al 2015].

At autopsy brain neurons may contain tau-associated neurofibrillary tangles [Maurage et al 2005, Oyamada et al 2006, Caillet-Boudin et al 2014].

Nerve. An axonal peripheral neuropathy may add to the weakness but may be uncommon [Krishnan & Kiernan 2006, Bae et al 2008]. Peric et al [2013] found evidence of neuropathy by nerve conduction studies in one third of 111 individuals with DM1.

Eye. Cataracts can eventually be observed as having characteristic multicolored “Christmas tree” appearance by slit lamp examination in nearly all affected individuals. They may cause visual symptoms at any age, but usually in the 30s-40s.

Some affected individuals have ophthalmoplegia.

Endocrine. Endocrinopathies including hyperinsulinism, thyroid dysfunction, diabetes mellitus, calcium dysregulation, testicular atrophy, and possible abnormalities in growth hormone secretion can be observed, although they are rarely clinically significant. Infertility may occur in otherwise asymptomatic persons [García de Andoin et al 2005, Matsumura et al 2009]. The largest published study of these endocrine abnormalities is that of Ørngreen et al [2012]. Secondary hyperparathyroidism with normal serum calcium and low 25-hydroxy vitamin D has been reported in up to 18% of affected persons [Passeri et al 2013].

Skin. Pilomatrixomata and epitheliomas can occur, especially on the scalp, and can be confused with sebaceous cysts [Geh & Moss 1999, Cigliano et al 2005, Zampetti et al 2015]. Androgenic alopecia is also common [Campanati et al 2015].

Cancer risk. Win et al [2012] found that individuals with DM1 may be at increased risk for thyroid cancer, choroidal melanoma, and possibly testicular and prostate cancers. There was no increased risk of cancer in non-DM relatives [Lund et al 2014]. Additional studies are needed.

Disease course. Rarely, after several decades of disease, DM1 progresses to the point of wheelchair confinement. Weakness/myotonia of the diaphragm and a susceptibility to aspiration increase the risk for respiratory compromise, usually in individuals with advanced disease [Roses 1997].

Several studies have evaluated life span and mortality in DM1 (Table 2) [de Die-Smulders et al 1998, Mathieu et al 1999]. The most common causes of death are pneumonia/respiratory failure, cardiovascular disease, sudden death/arrhythmia, and neoplasms [Benhayon et al 2015, Johnson et al 2015]. In the study of de Die-Smulders et al [1998] 50% of individuals with DM1 were either partially or totally wheelchair bound shortly before death. The cumulative probability of 15-year survival in Belgrade was 50% [Mladenovic et al 2006]. Both early age of onset and decreased survival correlate with larger CTG repeat expansions [Groh et al 2011].

Congenital DM1

A transmission ratio distortion at conception favors transmission of larger CTG repeats than those present in the parent [Dean et al 2006]. The mother is almost always the parent who transmits the larger repeat, although transmission by the father has been reported [Zeesman et al 2002]. Presence of a large repeat may lead to earlier onset and more severe disease, known as congenital DM1 [De Temmerman et al 2004, Rakocević-Stojanović et al 2005].

Prenatal. Congenital DM1 often presents before birth as polyhydramnios and reduced fetal movement.

Neonatal. After delivery, the main features are severe generalized weakness, hypotonia, and respiratory compromise. Typically, affected infants have an inverted V-shaped (also termed 'tented or 'fish'-shaped) upper lip, which is characteristic of significant facial diplegia (weakness). Mortality from respiratory failure is common.

Infancy and childhood. Surviving infants experience gradual improvement in motor function. Affected children are usually able to walk; however, a progressive myopathy occurs eventually, as in the classic form [Harper 2001]. These individuals may develop any of the typical features of DM1 including weakness, myotonia, cataracts, and cardiac problems.

  • Intellectual disability is present in 50%-60% of individuals with congenital DM1. The cause of the intellectual disability is unclear, but cerebral atrophy and ventricular dilation are often evident at birth. Intellectual disability may result from a combination of early respiratory failure and a direct effect of the DMPK pathogenic variant on the brain [Spranger et al 1997, Ekström et al 2009]. Autism spectrum disorder may be observed [Ekström et al 2008]. Douniol et al [2012] have reported common mood/anxiety disorders, impaired attention, and abnormal visual-spatial abilities.
  • Vision. Children with DM1 may have low visual acuity, hyperopia, or astigmatism [Ekström et al 2010].

Genotype-Phenotype Correlations

In general, longer CTG repeat expansions correlate with an earlier age of onset and more severe disease [Logigian et al 2004] (Table 2). Small but abnormal repeats (50-99) are often associated with a mild or asymptomatic phenotype [Arsenault et al 2006].

The DMPK CTG trinucleotide repeat length is mitotically unstable in individuals with DM1. Such instability very often leads to somatic mosaicism for the size of the CTG expansion; therefore, correlation between CTG repeat size observed in one tissue and disease severity may not be possible [Moxley & Meola 2008].

A person who was a compound heterozygote for expanded alleles with 1260 and 60 CTG repeats was reported to have cerebral abnormalities [Cerghet et al 2008].

Penetrance

Penetrance is high (nearly 100% by age 50 years) when all manifestations of the disease, even those that are subtle, are sought. However, mild cases (e.g., persons with only cataracts) may be missed [Moxley & Meola 2008].

Anticipation

Because DMPK alleles of CTG length greater than 34 repeats are unstable and may expand in length during meiosis, at-risk offspring may inherit repeat lengths considerably longer than those present in the transmitting parent. This phenomenon results in anticipation, the occurrence of increasing disease severity and decreasing age of onset in successive generations.

Most often a child with early-onset, severe DM1 (i.e., congenital DM1) has inherited the expanded DMPK allele from the mother [Harper 2001, Rakocević-Stojanović et al 2005, Martorell et al 2007]. Although anticipation typically occurs in maternal transmission of the disease, anticipation with paternal transmission is possible [Harper 2001, Moxley & Meola 2008].

Prevalence

Estimates of the prevalence of DM1 range from 1:100,000 in some areas of Japan to 1:10,000 in Iceland, with an overall estimated worldwide prevalence of 1:20,000 [Theadom et al 2014].

Founder effects may increase the prevalence in specific regions, such as Quebec [Yotova et al 2005, Pratte et al 2015].

Differential Diagnosis

The distinction between myotonic dystrophy type 1 (DM1) and other inherited myopathies is made by determining the number of CTG repeats in DMPK.

Myotonic dystrophy type 2 (DM2) is characterized by myotonia (90% of affected individuals) and muscle dysfunction (weakness, pain, and stiffness) (82%), and less commonly by cardiac conduction defects, iridescent posterior subcapsular cataracts, insulin-insensitive type 2 diabetes mellitus, and testicular failure. Although myotonia has been reported during the first decade, onset is typically in the third decade, most commonly with fluctuating or episodic muscle pain that can be debilitating and weakness of the neck flexors and finger flexors. Subsequently, weakness occurs in the elbow extensors and the hip flexors and extensors. Facial weakness and weakness of the ankle dorsiflexors are less common. Myotonia rarely causes severe symptoms. A detailed comparison between DM1 and DM2 has been reported [Turner & Hilton-Jones 2010]. DM2 is caused by mutation of CNBP. CNBP intron 1 contains a complex repeat motif, (TG)n(TCTG)n(CCTG)n. Expansion of the CCTG repeat causes DM2. Inheritance is autosomal dominant.

No other genetic causes of multisystem myotonic dystrophies have been identified, although they likely exist. The International Myotonic Dystrophy Consortium (IDMC) has agreed that any newly identified multisystem myotonic dystrophies will be sequentially named as forms of myotonic dystrophy.

One family posited to have DM3 [Le Ber et al 2004] was subsequently shown to have an unusual presentation of inclusion body myopathy with Paget disease and frontotemporal dementia (IBMPFTD) [Udd et al 2006], caused by mutation of VCP.

If the DMPK CTG repeat length is in the normal range and if DM2 has been excluded by molecular genetic testing of CNBP, further testing with EMG, serum CK concentration, and/or muscle biopsy is often warranted to evaluate for other causes of muscle disease.

The differential diagnosis for hereditary distal myopathies includes GNE-related myopathy (hereditary inclusion body myopathy 2), myofibrillar myopathy, distal muscular dystrophy (e.g., dysferlinopathy, Welander), and the limb-girdle muscular dystrophies.

Other hereditary disorders associated with myotonia are: myotonia congenita (also called Thomsen disease or Becker disease), caused by mutation of CLCN1; paramyotonia congenita (OMIM 168300) and its variants, caused by mutation of SCN4A; and hyperkalemic periodic paralysis, caused by mutation of SCN4A.

Occasionally, DM1 has been misdiagnosed as motor neuron disease (see Spinal Muscular Atrophy and Spinal and Bulbar Muscular Atrophy), cerebral palsy, nonspecific intellectual disability, or, because of 'masked face' and slow movements, parkinsonism.

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in adults with classic DM1, the following evaluations are recommended:

  • Baseline neurologic examination
  • Baseline examination by an ophthalmologist familiar with the iridescent posterior subcapsular cataract characteristic of DM1
  • Assessment of thyroid function
  • ECG, Holter monitoring, and echocardiogram to evaluate syncope, palpitations, and other symptoms of potential cardiac origin
  • Pulmonary function test
  • Assessment of strength [Whittaker et al 2006]
  • Assessment of cognitive ability
  • Fasting blood glucose determination
  • Consultation with a medical geneticist and/or genetic counselor

To establish the extent of disease and needs in children diagnosed with congenital myotonic dystrophy type 1 (DM1), the following evaluations are recommended:

  • Baseline neurologic examination
  • Baseline ophthalmologic examination
  • Assessment of motor skills
  • Assessment of cognitive ability
  • Baseline cardiac evaluation
  • Pulmonary function test
  • Baseline endocrine evaluation
  • Consultation with a medical geneticist and/or genetic counselor

Treatment of Manifestations

Management guidelines have been developed [Gagnon et al 2010].

No specific treatment exists for the progressive weakness in individuals with DM1.

A physiatrist, occupational therapist, or physical therapist can help evaluate affected individuals regarding the need for ankle-foot orthoses, wheelchairs, or other assistive devices as the disease progresses. Orthopedic surgery may benefit children with musculoskeletal deformities [Canavese & Sussman 2009].

Special education evaluation is indicated for children with DM1.

Increased weakness in DM1 has been associated with both hypothyroidism and certain cholesterol-lowering medications (i.e. statins); thus, some strength may return if these causative factors are eliminated.

Myotonia in DM1 is typically mild to moderate and rarely requires treatment [Ricker et al 1999]. Anecdotally, some individuals have responded to mexilitene or carbamazepine. Logigian et al [2010] found mexilitene 150-200 mg TID effective and safe for treating myotonia.

Pain management can be an important part of DM1 treatment. Different medications and combinations of medications work for some individuals, although none has been routinely effective; medications that have been used include mexilitene, gabapentin, nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose thyroid replacement, low-dose steroids, and tricyclic antidepressants. When used as part of a comprehensive pain management program, low-dose analgesics may provide relief.

Consultation with a cardiologist is appropriate for individuals with cardiac symptoms or ECG evidence of arrhythmia because fatal arrhythmias can occur prior to other symptoms in individuals with DM1. More advanced, invasive electrophysiologic testing of the heart may be required [Sovari et al 2007].

Cataracts can be removed if they impair vision. Recurrence after surgery has been reported [Garrott et al 2004].

Males with low serum concentration of testosterone require hormone replacement therapy if they are symptomatic.

In most cases, surgical excision of pilomatrixoma including clear margins and its overlying skin is the preferred treatment [Cigliano et al 2005].

An extensive review found no evidence for successful treatment of hypersomnia with routine psychostimulants [Annane et al 2006], although others have reported benefit [Talbot et al 2003, Wintzen et al 2007].

Prevention of Secondary Complications

Veyckemans & Scholtes [2013] have reviewed the anesthetic management of individuals with DM1. Choice of induction agents, airway care, local anesthesia, and neuromuscular blockade were found to minimize complications during surgery in individuals with DM1. Avoid using succinylcholine. Propofol-induced pain can induce myotonia. Sevoflurane has been used uneventfully.

Cardiac pacemakers or implantable cardioverter-defibrillators may prevent life-threatening arrhythmias [Wahbi et al 2012, Facenda-Lorenzo et al 2013].

Gagnon et al [2013] presented evidence that obesity, tobacco smoking, physical inactivity and alcohol/illicit drug consumption are lifestyle risk factors associated with more severe DM1 phenotypes.

Surveillance

Gagnon et al [2010] provide guidelines for surveillance.

The following are appropriate:

Agents/Circumstances to Avoid

Statins used to lower cholesterol may sometimes cause muscle pain and weakness.

Mathieu et al [1997] noted that “[n]umerous cases of perioperative complications in patients with DM have been reported. Hazards have been associated with the use of thiopentone, suxamethonium, neostigmine, and halothane. A retrospective study of perioperative complications was conducted for 219 patients who had their first surgery under general anesthesia at the Chicoutimi Hospital. The overall frequency of complications was 8.2% (18 of 219). Most complications (16 of 18) were pulmonary, including five patients with acute ventilatory failure necessitating ventilatory support, four patients with atelectasis, and three patients with pneumonia. Using multivariate analysis, [the authors] found that the risk of perioperative pulmonary complications (PPC) was significantly higher after an upper abdominal surgery and for patients with a severe muscular disability, as assessed by the presence of proximal limb weakness. The likelihood of PPC was not related to any specific anesthetic drug. Because of the increased risk of PPC, careful monitoring during the early postoperative period, protection of the upper airways, chest physiotherapy, and incentive spirometry are mandatory in all symptomatic patients with DM, particularly those with a severe muscular disability or those who have undergone an upper abdominal surgery.”

Veyckemans & Scholtes [2013] have reviewed appropriate anesthetic care for patients with DM1 and DM2.

Malignant hyperthermia during anesthesia including the use of vecuronium [Nishi et al 2004] has been reported in DM1 but is very uncommon [Kirzinger et al 2010]. (See Malignant Hyperthermia Susceptibility.)

Aggressive doxorunbicin-based chemotherapy for lymphoma in a person with DM1 produced sudden atrial fibrillations [Montella et al 2005].

Evaluation of Relatives at Risk

It is appropriate to clarify the genetic status of apparently asymptomatic at-risk adult relatives of an affected individual to allow for early diagnosis and treatment of cardiac manifestations, diabetes mellitus, and cataracts.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

Women with DM1 are at risk for complications during pregnancy including increased spontaneous abortion rate, premature labor, prolonged labor, retained placenta, placenta previa, and postpartum hemorrhage [Zaki et al 2007, Argov & de Visser 2009]. Special surveillance during pregnancy of women with DM1 includes ultrasound examination; evaluation for placenta previa; and anticipation of possible polyhydramnios, prolonged labor, and/or need for delivery by cesarean section [Argov & de Visser 2009]. Complications related to the presence of congenital DM1 in the fetus include reduced fetal movement and polyhydramnios. Awater et al [2012] found increased rates of caesarean birth and preterm delivery among women with DM1.

Therapies Under Investigation

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions.

Other

Moderate-intensity strength training does no harm, but it is unclear whether it offers measurable benefits [van der Kooi et al 2005]. A controlled study of an exercise program for DM1 showed neither beneficial nor detrimental effects [Kierkegaard et al 2011].

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Myotonic dystrophy type 1 (DM1) is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

  • Virtually all individuals with DM1 have inherited their expanded CTG allele from a parent who also has an allele in the abnormal range (>34 CTG repeats).
  • New expansions of a normal allele (≤34 CTG repeats) into the abnormal range are rare.
  • Some individuals diagnosed with DM1 have an obviously affected parent; others do not. The parent may appear to be unaffected because of failure to recognize symptoms of mild DM1, or the parent may have no symptoms and have an abnormal, but small, CTG repeat expansion.

    When the parents of a proband are unaffected and do not have a CTG expansion in the abnormal range (>34 repeats), possible non-medical explanations including alternate paternity or maternity (e.g., with assisted reproduction) or undisclosed adoption could be explored.
  • If both parents of a proband are asymptomatic, it is appropriate to offer DMPK molecular genetic testing to both for the purpose of genetic counseling of other family members. In this instance, genetic counseling issues relevant to presymptomatic testing should be addressed.

Sibs of a proband

  • The risk to sibs of a proband depends on the genetic status of the parents.
  • If one parent has an expanded DMPK allele, the risk to each sib is 50%.

Offspring of a proband

  • All offspring of an individual with an expanded DMPK allele (>34 CTG repeats) have a 50% chance of inheriting the expanded DMPK allele.
  • An expanded DMPK allele may expand further in length during gametogenesis, resulting in transmission of an allele with a larger CTG repeat that may be associated with earlier onset and more severe disease than that in the parent. In a recent study of children of parents with small expansions (50-100 CTG repeats), those with expanded alleles transmitted paternally had a larger increase in CTG repeats (median, 425 repeats; range, 70-2000) than did those with maternally transmitted expanded alleles (median, 200 repeats; range, 57-1400) [Pratte et al 2015].

Other family members

  • The risk to other family members depends on the status of the proband's parent.
  • If a parent is affected or has a CTG expansion in the abnormal range (>34 repeats), his or her family members are at risk.

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.

Empiric risks for congenital DM1. Data concerning the likelihood that a mother with a particular CTG repeat size will have a child with a particular CTG repeat size or phenotype may be useful in recurrence risk counseling. The available data have wide confidence limits, making specific risk estimates difficult.

  • Redman et al [1993] found that for women with a CTG repeat length of 100 or higher, the risk to a child who has inherited the abnormal allele of having an expansion of 730 or more CTG repeats (and thus congenital DM1) is 62%. Martorell et al [2007] found a similar frequency of 63% of fetuses with more than 1000 repeats in 31 of 49 maternal transmissions of the expanded allele (mothers’ abnormal allele size ranging from 65 to 1333 CTG repeats).
  • Cobo et al [1995] determined that for women with a CTG repeat size smaller than 300, the risk to a child who has inherited the abnormal allele of having congenital DM1 is 10%, and for women with a CTG repeat size greater than 300, the risk to a child who has inherited the abnormal allele of having congenital DM1 is 59%. Martorell et al [2007] found a similar correlation, but there was no statistical analysis.

Diagnosis of mildly affected individuals during family evaluation. Individuals with mild DM1 are often unaware of having DM1 and may only be diagnosed in the course of evaluation of a more severely affected family member. This often occurs when an asymptomatic mother having a CTG repeat size under 100 gives birth to an infant with congenital DM1 with a CTG repeat length in the thousands.

Testing of at-risk asymptomatic adult relatives of individuals with DM1 is possible after molecular genetic testing has identified the expanded DMPK allele in an affected family member. Such testing should be performed in the context of formal genetic counseling and is not useful in predicting age of onset, severity, type of symptoms, or rate of progression in asymptomatic individuals. Testing of asymptomatic at-risk individuals with nonspecific or equivocal symptoms is predictive testing, not diagnostic testing.

Testing of asymptomatic individuals younger than age 18 years who are at risk for adult-onset disorders for which no treatment exists is not considered appropriate, primarily because it negates the autonomy of the child with no compelling benefit. Further, concern exists regarding the potential unhealthy adverse effects that such information may have on family dynamics, the risk of discrimination and stigmatization in the future, and the anxiety that such information may cause.

Testing is appropriate to consider in symptomatic individuals in a family with an established diagnosis of DM1 regardless of age.

For more information, see the National Society of Genetic Counselors position statement on genetic testing of minors for adult-onset conditions and the American Academy of Pediatrics and American College of Medical Genetics and Genomics policy statement: ethical and policy issues in genetic testing and screening of children.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

A priori high risk. If an expanded DMPK allele has been identified in an affected family member, prenatal testing for pregnancies at 50% risk for DM1 may be available from a clinical laboratory that offers either testing of this gene or custom prenatal testing.

Note: (1) Abnormal test results do not predict the age of onset or severity of the disease because of the overlap of CTG repeat length associated with the three phenotypes and the possibility of somatic mosaicism for the size of the CTG expansion. However, CTG repeat lengths 730-1000 or greater are more likely to be associated with congenital DM1 [Redman et al 1993, Martorell et al 2007]. (2) Ultrasound examination in the second and third trimesters may reveal decreased fetal movement and polyhydramnios, possible indicators of congenital DM1.

A priori low risk. For fetuses not known to be at increased risk for DM1, molecular genetic testing for an expanded DMPK allele may be considered if polyhydramnios and/or decreased fetal activity are observed on ultrasound examination in the third trimester.

Preimplantation genetic diagnosis (PGD) may be an option for some families in which an expanded DMPK allele has been identified [Kakourou et al 2008]. No effect of trinucleotide repeat size on reproductive outcome in PGD was observed in 78 couples in which 54 females and 24 males had DM1 [Verpoest et al 2010]. In these individuals the CTG repeat size ranged from 50 to 1330 with a mean of 410. The cumulative delivery rate was 46% in 205 cycles [Verpoest et al 2008].

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Myotonic Dystrophy: Making an Informed Choice About Genetic Testing
    Booklet providing information about Myotonic Dystrophy and genetic testing (PDF file)
    University of Washington Medical Center, Medical Genetics and Neurology
    Seattle WA
  • National Library of Medicine Genetics Home Reference
  • NCBI Genes and Disease
  • Muscular Dystrophy Association - USA (MDA)
    222 South Riverside Plaza
    Suite 1500
    Chicago IL 60606
    Phone: 800-572-1717
    Email: mda@mdausa.org
  • Muscular Dystrophy Campaign
    61A Great Suffolk Street
    London SE1 0BU
    United Kingdom
    Phone: 0800 652 6352 (toll-free); 020 7803 4800
    Email: info@muscular-dystrophy.org
  • Myotonic Dystrophy Family Registry (MDFR)
    Phone: 602-435-7496
    Email: coordinator@myotonicregistry.org
  • National Registry of Myotonic Dystrophy and FSHD Patients and Family Members
    National Registry of Myotonic Dystrophy and FSHD
    601 Elmwood Avenue
    Box 673
    Rochester NY 14642
    Phone: 888-925-4302
    Fax: 585-273-1255
    Email: dystrophy_registry@urmc.rochester.edu

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Myotonic Dystrophy Type 1: Genes and Databases

GeneChromosome LocusProteinLocus SpecificHGMD
DMPK19q13​.32Myotonin-protein kinaseDMPK databaseDMPK

Data are compiled from the following standard references: gene from HGNC; chromosome locus, locus name, critical region, complementation group from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B.

OMIM Entries for Myotonic Dystrophy Type 1 (View All in OMIM)

160900MYOTONIC DYSTROPHY 1; DM1
605377DYSTROPHIA MYOTONICA PROTEIN KINASE; DMPK

Gene structure. DMPK has 14 exons covering approximately 13 kb of genomic DNA. For a detailed summary of gene and protein information, see Table A, Gene.

Benign allelic variants. Normal allelic variants have 5-34 CTG repeats. Alleles with 35-49 CTG repeats are mutable normal (or premutation) alleles. Individuals with CTG expansions in the premutation range have not been reported to have symptoms, but their children are at increased risk of inheriting a larger repeat size and thus having symptoms [Martorell et al 2001].

Pathogenic allelic variants. Myotonic dystrophy type 1 (DM1) appears to be caused by a single mutational mechanism: expanded CTG trinucleotide repeat (>49). Other types of pathogenic variants (e.g., single nucleotide variants, deletions, insertions) in DMPK have not been reported to be associated with DM1. The CTG repeat that is expanded in DM1 lies in the 3' untranslated region of DMPK. Abnormal repeat lengths may reach several thousand, particularly in individuals with congenital DM1.

Table 3.

Selected DMPK Allelic Variants

Variant
Classification
DNA Nucleotide ChangeProtein Amino
Acid Change
Reference
Sequences
Benignc.*224_226CTG(5-34) 1
(normal range 5-34 CTG repeats)
NANM_001081563​.1
NP_001075032​.1
c.*224_226CTG(35-49) 1
(mutable normal range 35-49 CTG repeats)
Pathogenicc.*224_226CTG(50-?) 1
(full-penetrance mutated alleles >50 CTG repeats)

Note on variant classification: Variants listed in the table have been provided by the author. GeneReviews staff have not independently verified the classification of variants.

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (www​.hgvs.org). See Quick Reference for an explanation of nomenclature.

NA = not applicable

1.

The CTG variant is in the 3’untranslated region of the gene (indicated by *), with the first nucleotide after the stop codon numbered as *1. Parentheses indicate the range of numbers of the CTG repeats, here indicating normal alleles range from 5-34 repeats. A specific single allele with five repeats would be designated as c.*224_226CTG[5].

Normal gene product. Myotonin-protein kinase (DMPK), a 69-kd serine-threonine protein kinase, has been localized to specialized cell structures in heart and skeletal muscle that are associated with intercellular conduction and impulse transmission. It is closely related to cyclic-AMP-dependent protein kinases and to Rho-binding kinases. DMPK may interact with a GTP-binding protein that is a regulatory subunit of myosin phosphatase.

Abnormal gene product. The effect of the CTG repeat remains complex and many issues are being clarified [Fiszer & Krzyzosiak 2013, Meola & Cardani 2015]. The effects of an expanded CTG repeat may occur via abnormal RNA transcript processing. Two homologous RNA CUG-binding proteins (CUG-BP and MBNL1 [muscleblind]) have been identified. These proteins are mutually antagonistic mediators of a subgroup of alternative splicing events that are disrupted in DM, in which embryonic forms of some proteins now predominate. These proteins include: a chloride channel, resulting in myotonia; the insulin receptor, resulting in increased risk of diabetes mellitus; and microtubule-associated protein tau, encoded by MAPT, a gene associated with cognitive function [Savkur et al 2001, Mankodi et al 2002, Kanadia et al 2003, Ranum & Day 2004, Day & Ranum 2005, Cooper 2006, Leroy et al 2006, Wheeler & Thornton 2007, Carpentier et al 2014, Echeverria & Cooper 2014]. There is considerable somatic mosaicism between various organs in DM1.

References

Published Guidelines/Consensus Statements

  1. Committee on Bioethics, Committee on Genetics, and American College of Medical Genetics and Genomics Social, Ethical, Legal Issues Committee. Ethical and policy issues in genetic testing and screening of children. Available online. 2013. Accessed 10-22-15. [PubMed: 23428972]
  2. International Myotonic Dystrophy Consortium. New nomenclature and DNA testing guidelines for myotonic dystrophy type 1 (DM1). Available online (registration or institutional access required). 2000. Accessed 10-22-15.
  3. National Society of Genetic Counselors. Position statement on genetic testing of minors for adult-onset disorders. Available online. 2012. Accessed 10-22-15.
  4. Prior TW; American College of Medical Genetics (ACMG) Laboratory Quality Assurance Committee. Technical standards and guidelines for myotonic dystrophy type 1 testing. Available online. 2009. Accessed 10-22-15. [PubMed: 19546810]

Literature Cited

  1. Annane D, Moore DH, Barnes PR, Miller RG. Psychostimulants for hypersomnia (excessive daytime sleepiness) in myotonic dystrophy. Cochrane Database Syst Rev. 2006;3:CD003218. [PubMed: 16855999]
  2. Antonini G, Soscia F, Giubilei F, De Carolis A, Gragnani F, Morino S, Ruberto A, Tatarelli R. Health-related quality of life in myotonic dystrophy type 1 and its relationship with cognitive and emotional functioning. J Rehabil Med. 2006;38:181–5. [PubMed: 16702085]
  3. Argov Z, de Visser M. What we do not know about pregnancy in hereditary neuromuscular disorders. Neuromuscul Disord. 2009;19:675–9. [PubMed: 19692244]
  4. Arsenault ME, Prevost C, Lescault A, Laberge C, Puymirat J, Mathieu J. Clinical characteristics of myotonic dystrophy type 1 patients with small CTG expansions. Neurology. 2006;66:1248–50. [PubMed: 16636244]
  5. Awater C, Zerres K, Rudnik-Schöneborn S. Pregnancy course and outcome in women with hereditary neuromuscular disorders: comparison of obstetric risks in 178 patients. Eur J Obstet Gynecol Reprod Biol. 2012;162:153–9. [PubMed: 22459654]
  6. Bae JS, Kim OK, Kim SJ, Kim BJ. Abnormalities of nerve conduction studies in myotonic dystrophy type 1: primary involvement of nerves or incidental coexistence? J Clin Neurosci. 2008;15:1120–4. [PubMed: 18657426]
  7. Bassez G, Lazarus A, Desguerre I, Varin J, Laforet P, Becane HM, Meune C, Arne-Bes MC, Ounnoughene Z, Radvanyi H, Eymard B, Duboc D. Severe cardiac arrhythmias in young patients with myotonic dystrophy type 1. Neurology. 2004;63:1939–41. [PubMed: 15557517]
  8. Bellini M, Biagi S, Stasi C, Costa F, Mumolo MG, Ricchiuti A, Marchi S. Gastrointestinal manifestations in myotonic muscular dystrophy. World J Gastroenterol. 2006;12:1821–8. [PMC free article: PMC4087506] [PubMed: 16609987]
  9. Benhayon D, Lugo R, Patel R, Carballeira L, Elman L, Cooper JM. Long-term arrhythmia follow-up of patients with myotonic dystrophy. J Cardiovasc Electrophysiol. 2015;26:305–10. [PubMed: 25546341]
  10. Bertrand JA, Jean S, Laberge L, Gagnon C, Mathieu J, Gagnon JF, Richer L. Psychological characteristics of patients with myotonic dystrophy type 1. Acta Neurol Scand. 2015;132:49–58. [PubMed: 25496310]
  11. Bouchard JP, Cossette L, Bassez G, Puymirat J. Natural history of skeletal muscle involvement in myotonic dystrophy type 1: a retrospective study in 204 cases. J Neurol. 2015;262:285–93. [PubMed: 25380585]
  12. Breton R, Mathieu J. Usefulness of clinical and electrocardiographic data for predicting adverse cardiac events in patients with myotonic dystrophy. Can J Cardiol. 2009;25:e23–7. [PMC free article: PMC2691914] [PubMed: 19214296]
  13. Caillet-Boudin ML, Fernandez-Gomez FJ, Tran H, Dhaenens CM, Buee L, Sergeant N. Brain pathology in myotonic dystrophy: when tauopathy meets spliceopathy and RNAopathy. Front Mol Neurosci. 2014;6:57. [PMC free article: PMC3885824] [PubMed: 24409116]
  14. Campanati A, Giannoni M, Buratti L, Cagnetti C, Giuliodori K, Ganzetti G, Silvestrini M, Provinciali L, Offidani A. Skin features in myotonic dystrophy type 1: an observational study. Neuromuscul Disord. 2015;25:409–13. [PubMed: 25813338]
  15. Canavese F, Sussman MD. Orthopaedic manifestations of congenital myotonic dystrophy during childhood and adolescence. J Pediatr Orthop. 2009;29:208–13. [PubMed: 19352249]
  16. Carpentier C, Ghanem D, Fernandez-Gomez FJ, Jumeau F, Philippe JV, Freyermuth F, Labudeck A, Eddarkaoui S, Dhaenens CM, Holt I, Behm-Ansmant I, Marmier-Gourrier N, Branlant C, Charlet-Berguerand N, Marie J, Schraen-Maschke S, Buée L, Sergeant N, Caillet-Boudin ML. Tau exon 2 responsive elements deregulated in myotonic dystrophy type I are proximal to exon 2 and synergistically regulated by MBNL1 and MBNL2. Biochim Biophys Acta. 2014;1842:654-64. [PubMed: 24440524]
  17. Caso F, Agosta F, Peric S, Rakočević-Stojanović V, Copetti M, Kostic VS, Filippi M. Cognitive impairment in myotonic dystrophy type 1 is associated with white matter damage. PLoS One. 2014;9:e104697. [PMC free article: PMC4130603] [PubMed: 25115999]
  18. Cerghet M, Tapos D, Serajee FJ, Mahbubul Huq AH. Homozygous myotonic dystrophy with craniosynostosis. J Child Neurol. 2008;23:930–3. [PubMed: 18474935]
  19. Chebel S, Ben Hamda K, Boughammoura A, Frih Ayed M, Ben Farhat MH. Cardiac involvement in Steinert's myotonic dystrophy. Rev Neurol (Paris) 2005;161:932–9. [PubMed: 16365622]
  20. Cigliano B, Baltogiannis N, De Marco M, Faviou E, Settimi A, Tilemis S, Soutis M, Papandreou E, D'Agostino S, Fabbro MA. Pilomatricoma in childhood: a retrospective study from three European paediatric centres. Eur J Pediatr. 2005;164:673–7. [PubMed: 16041525]
  21. Cobo AM, Poza JJ, Martorell L, Lopez de Munain A, Emparanza JI, Baiget M. Contribution of molecular analyses to the estimation of the risk of congenital myotonic dystrophy. J Med Genet. 1995;32:105–8. [PMC free article: PMC1050229] [PubMed: 7760317]
  22. Cooper TA. A reversal of misfortune for myotonic dystrophy? N Engl J Med. 2006;355:1825–7. [PubMed: 17065646]
  23. Cudia P, Bernasconi P, Chiodelli R, Mangiola F, Bellocci F, Dello Russo A, Angelini C, Romeo V, Melacini P, Politano L, Palladino A, Nigro G, Siciliano G, Falorni M, Bongiorni MG, Falcone C, Mantegazza R, Morandi L. Risk of arrhythmia in type I myotonic dystrophy: the role of clinical and genetic variables. J Neurol Neurosurg Psychiatry. 2009;80:790–3. [PubMed: 19237383]
  24. Dauvilliers YA, Laberge L. Myotonic dystrophy type 1, daytime sleepiness and REM sleep dysregulation. Sleep Med Rev. 2012;16:539–45. [PubMed: 22465566]
  25. Day JW, Ranum LP. RNA pathogenesis of the myotonic dystrophies. Neuromuscul Disord. 2005;15:5–16. [PubMed: 15639115]
  26. de Die-Smulders CE, Howeler CJ, Thijs C, Mirandolle JF, Anten HB, Smeets HJ, Chandler KE, Geraedts JP. Age and causes of death in adult-onset myotonic dystrophy. Brain. 1998;121:1557–63. [PubMed: 9712016]
  27. de Swart BJ, van Engelen BG, van de Kerkhof JP, Maassen BA. Myotonia and flaccid dysarthria in patients with adult onset myotonic dystrophy. J Neurol Neurosurg Psychiatry. 2004;75:1480–2. [PMC free article: PMC1738733] [PubMed: 15377703]
  28. De Temmerman N, Sermon K, Seneca S, De Rycke M, Hilven P, Lissens W, Van Steirteghem A, Liebaers I. Intergenerational instability of the expanded CTG repeat in the DMPK gene: studies in human gametes and preimplantation embryos. Am J Hum Genet. 2004;75:325–9. [PMC free article: PMC1216067] [PubMed: 15185171]
  29. Dean NL, Loredo-Osti JC, Fujiwara TM, Morgan K, Tan SL, Naumova AK, Ao A. Transmission ratio distortion in the myotonic dystrophy locus in human preimplantation embryos. Eur J Hum Genet. 2006;14:299–306. [PubMed: 16391559]
  30. Delaporte C. Personality patterns in patients with myotonic dystrophy. Arch Neurol. 1998;55:635–40. [PubMed: 9605719]
  31. Dello Russo A, Pelargonio G, Parisi Q, Santamaria M, Messano L, Sanna T, Casella M, De Martino G, De Ponti R, Pace M, Giglio V, Ierardi C, Zecchi P, Crea F, Bellocci F. Widespread electroanatomic alterations of right cardiac chambers in patients with myotonic dystrophy type 1. J Cardiovasc Electrophysiol. 2006;17:34–40. [PubMed: 16426397]
  32. Douniol M, Jacquette A, Cohen D, Bodeau N, Rachidi L, Angeard N, Cuisset JM, Vallée L, Eymard B, Plaza M, Héron D, Guilé JM. Psychiatric and cognitive phenotype of childhood myotonic dystrophy type 1. Dev Med Child Neurol. 2012;54:905–11. [PubMed: 22861906]
  33. Echeverria GV, Cooper TA. Muscleblind-like 1 activates insulin receptor exon 11 inclusion by enhancing U2AF65 binding and splicing of the upstream intron. Nucleic Acids Res. 2014;42:1893–903. [PMC free article: PMC3919616] [PubMed: 24185704]
  34. Ekström AB, Hakenäs-Plate L, Samuelsson L, Tulinius M, Wentz E. Autism spectrum conditions in myotonic dystrophy type 1: a study on 57 individuals with congenital and childhood forms. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:918–26. [PubMed: 18228241]
  35. Ekström AB, Hakenäs-Plate L, Tulinius M, Wentz E. Cognition and adaptive skills in myotonic dystrophy type 1: a study of 55 individuals with congenital and childhood forms. Dev Med Child Neurol. 2009;51:982–90. [PubMed: 19459914]
  36. Ekström AB, Tulinius M, Sjöström A, Aring E. Visual function in congenital and childhood myotonic dystrophy type 1. Ophthalmology. 2010;117:976–82. [PubMed: 20346513]
  37. Engvall M, Sjögreen L, Kjellberg H, Robertson A, Sundell S, Kiliaridis S. Oral health status in a group of children and adolescents with myotonic dystrophy type 1 over a 4-year period. Int J Paediatr Dent. 2009;19:412–22. [PubMed: 19732192]
  38. Ercolin B, Sassi FC, Mangilli LD, Mendonça LI, Limongi SC, de Andrade CR. Oral motor movements and swallowing in patients with myotonic dystrophy type 1. Dysphagia. 2013;28:446–54. [PubMed: 23460343]
  39. Facenda-Lorenzo M, Hernández-Afonso J, Rodríguez-Esteban M, de León-Hernández JC, Grillo-Pérez JJ. Cardiac Manifestations in Myotonic Dystrophy Type 1 Patients Followed Using a Standard Protocol in a Specialized Unit. Rev Esp Cardiol. 2013;66:193–7. [PubMed: 24775453]
  40. Fiszer A, Krzyzosiak WJ. RNA toxicity in polyglutamine disorders: concepts, models, and progress of research. J Mol Med (Berl) 2013;91:683–91. [PMC free article: PMC3659269] [PubMed: 23512265]
  41. García de Andoin N, Echeverría J, Cobo AM, Rey A, Paisán L, López de Munain A. A neonatal form of Steinert's myotonic dystrophy in twins after in vitro fertilization. Fertil Steril. 2005;84:756. [PubMed: 16169416]
  42. Gagnon C, Chouinard MC, Laberge L, Brisson D, Gaudet D, Lavoie M, Leclerc N, Mathieu J. Prevalence of lifestyle risk factors in myotonic dystrophy type 1. Can J Neurol Sci. 2013;40:42–7. [PubMed: 23250126]
  43. Gagnon C, Chouinard MC, Laberge L, Veillette S, Bégin P, Breton R, Jean S, Brisson D, Gaudet D, Mathieu J., DMI Expert Panel. Health supervision and anticipatory guidance in adult myotonic dystrophy type 1. Neuromuscul Disord. 2010;20:847–51. [PubMed: 20884209]
  44. Garrott HM, Walland MJ, O'Day J. Recurrent posterior capsular opacification and capsulorhexis contracture after cataract surgery in myotonic dystrophy. Clin Experiment Ophthalmol. 2004;32:653–5. [PubMed: 15575838]
  45. Gaul C, Schmidt T, Windisch G, Wieser T, Muller T, Vielhaber S, Zierz S, Leplow B. Subtle cognitive dysfunction in adult onset myotonic dystrophy type 1 (DM1) and type 2 (DM2). Neurology. 2006;67:350–2. [PubMed: 16864839]
  46. Geh JL, Moss AL. Multiple pilomatrixomata and myotonic dystrophy: a familial association. Br J Plast Surg. 1999;52:143–5. [PubMed: 10434894]
  47. Gharehbaghi-Schnell EB, Finsterer J, Korschineck I, Mamoli B, Binder BR. Genotype-phenotype correlation in myotonic dystrophy. Clin Genet. 1998;53:20–6. [PubMed: 9550357]
  48. Glaser AM, Johnston JH, Gleason WA, Rhoads JM. Myotonic dystrophy as a cause of colonic pseudoobstruction: not just another constipated child. Clin Case Rep. 2015;3:424–6. [PMC free article: PMC4498855] [PubMed: 26185641]
  49. Groh WJ, Groh MR, Shen C, Monckton DG, Bodkin CL, Pascuzzi RM. Survival and CTG repeat expansion in adults with myotonic dystrophy type 1. Muscle Nerve. 2011;43:648–51. [PubMed: 21484823]
  50. Harper PS. Major Problems in Neurology: Myotonic Dystrophy. London, UK: WB Saunders; 2001.
  51. Heatwole CR, Miller J, Martens B, Moxley RT 3rd. Laboratory abnormalities in ambulatory patients with myotonic dystrophy type 1. Arch Neurol. 2006;63:1149–53. [PubMed: 16908743]
  52. International Myotonic Dystrophy Consortium. New nomenclature and DNA testing guidelines for myotonic dystrophy type 1 (DM1). The International Myotonic Dystrophy Consortium (IDMC). Neurology. 2000;54:1218–21. [PubMed: 10746587]
  53. Jean S, Richer L, Laberge L, Mathieu J. Comparisons of intellectual capacities between mild and classic adult-onset phenotypes of myotonic dystrophy type 1 (DM1). Orphanet J Rare Dis. 2014;9:186. [PMC free article: PMC4247010] [PubMed: 25424323]
  54. Johnson NE, Abbott D, Cannon-Albright LA. Relative risks for comorbidities associated with myotonic dystrophy: A population-based analysis. Muscle Nerve. 2015;52:659–61. [PMC free article: PMC4580516] [PubMed: 26172955]
  55. Kakourou G, Dhanjal S, Mamas T, Gotts S, Doshi A, Fordham K, Serhal P, Ranieri DM, Delhanty JD, Harper JC, SenGupta SB. Preimplantation genetic diagnosis for myotonic dystrophy type 1 in the UK. Neuromuscul Disord. 2008;18:131–6. [PubMed: 18053720]
  56. Kalkman JS, Schillings ML, van der Werf SP, Padberg GW, Zwarts MJ, van Engelen BG, Bleijenberg G. Experienced fatigue in facioscapulohumeral dystrophy, myotonic dystrophy, and HMSN-I. J Neurol Neurosurg Psychiatry. 2005;76:1406–9. [PMC free article: PMC1739364] [PubMed: 16170086]
  57. Kamsteeg EJ, Kress W, Catalli C, Hertz JM, Witsch-Baumgartner M, Buckley MF, van Engelen BG, Schwartz M, Scheffer H. Best practice guidelines and recommendations on the molecular diagnosis of myotonic dystrophy types 1 and 2. Eur J Hum Genet. 2012;20:1203–8. [PMC free article: PMC3499739] [PubMed: 22643181]
  58. Kanadia RN, Johnstone KA, Mankodi A, Lungu C, Thornton CA, Esson D, Timmers AM, Hauswirth WW, Swanson MS. A muscleblind knockout model for myotonic dystrophy. Science. 2003;302:1978–80. [PubMed: 14671308]
  59. Kierkegaard M, Harms-Ringdahl K, Edström L, Widén Holmqvist L, Tollbäck A. Feasibility and effects of a physical exercise programme in adults with myotonic dystrophy type 1: a randomized controlled pilot study. J Rehabil Med. 2011;43:695–702. [PubMed: 21670942]
  60. Kirzinger L, Schmidt A, Kornblum C, Schneider-Gold C, Kress W, Schoser B. Side effects of anesthesia in DM2 as compared to DM1: a comparative retrospective study. Eur J Neurol. 2010;17:842–5. [PubMed: 20100232]
  61. Krishnan AV, Kiernan MC. Axonal function and activity-dependent excitability changes in myotonic dystrophy. Muscle Nerve. 2006;33:627–36. [PubMed: 16453325]
  62. Kumar SP, Sword D, Petty RK, Banham SW, Patel KR. Assessment of sleep studies in myotonic dystrophy. Chron Respir Dis. 2007;4:15–8. [PubMed: 17416148]
  63. Laberge L, Bégin P, Dauvilliers Y, Beaudry M, Laforte M, Jean S, Mathieu J. A polysomnographic study of daytime sleepiness in myotonic dystrophy type 1. J Neurol Neurosurg Psychiatry. 2009;80:642–6. [PubMed: 19211594]
  64. Lau JK, Sy RW, Corbett A, Kritharides L. Myotonic dystrophy and the heart: A systematic review of evaluation and management. Int J Cardiol. 2015;184:600–8. [PubMed: 25769007]
  65. Le Ber I, Martinez M, Campion D, Laquerriere A, Betard C, Bassez G, Girard C, Saugier-Veber P, Raux G, Sergeant N, Magnier P, Maisonobe T, Eymard B, Duyckaerts C, Delacourte A, Frebourg T, Hannequin D. A non-DM1, non-DM2 multisystem myotonic disorder with frontotemporal dementia: phenotype and suggestive mapping of the DM3 locus to chromosome 15q21-24. Brain. 2004;127:1979–92. [PubMed: 15215218]
  66. Leroy O, Wang J, Maurage CA, Parent M, Cooper T, Buée L, Sergeant N, Andreadis A, Caillet-Boudin ML. Brain-specific change in alternative splicing of Tau exon 6 in myotonic dystrophy type 1. Biochim Biophys Acta. 2006;2006;1762:460–7. [PubMed: 16487687]
  67. Logigian EL, Blood CL, Dilek N, Martens WB, Moxley RT 4th, Wiegner AW, Thornton CA, Moxley RT 3rd. Quantitative analysis of the "warm-up" phenomenon in myotonic dystrophy type 1. Muscle Nerve. 2005;32:35–42. [PubMed: 15880468]
  68. Logigian EL, Martens WB, Moxley RT 4th, McDermott MP, Dilek N, Wiegner AW, Pearson AT, Barbieri CA, Annis CL, Thornton CA, Moxley RT 3rd. Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1. Neurology. 2010;2010;74:1441–8. [PMC free article: PMC2871004] [PubMed: 20439846]
  69. Logigian EL, Moxley RT 4th, Blood CL, Barbieri CA, Martens WB, Wiegner AW, Thornton CA, Moxley RT 3rd. Leukocyte CTG repeat length correlates with severity of myotonia in myotonic dystrophy type 1. Neurology. 2004;62:1081–9. [PubMed: 15079005]
  70. Lund M, Diaz LJ, Gørtz S, Feenstra B, Duno M, Juncker I, Eiberg H, Vissing J, Wohlfahrt J, Melbye M. Risk of cancer in relatives of patients with myotonic dystrophy: a population-based cohort study. Eur J Neurol. 2014;21:1192–7. [PubMed: 24838088]
  71. Mankodi A, Takahashi MP, Jiang H, Beck CL, Bowers WJ, Moxley RT, Cannon SC, Thornton CA. Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy. Mol Cell. 2002;10:35–44. [PubMed: 12150905]
  72. Martorell L, Cobo AM, Baiget M, Naudó M, Poza JJ, Parra J. Prenatal diagnosis in myotonic dystrophy type 1. Thirteen years of experience: implications for reproductive counselling in DM1 families. Prenat Diagn. 2007;2007;27:68–72. [PubMed: 17154336]
  73. Martorell L, Monckton DG, Sanchez A, Lopez De Munain A, Baiget M. Frequency and stability of the myotonic dystrophy type 1 premutation. Neurology. 2001;56:328–35. [PubMed: 11171897]
  74. Mathieu J, Allard P, Gobeil G, Girard M, De Braekeleer M, Begin P. Anesthetic and surgical complications in 219 cases of myotonic dystrophy. Neurology. 1997;49:1646–50. [PubMed: 9409361]
  75. Mathieu J, Allard P, Potvin L, Prevost C, Begin P. A 10-year study of mortality in a cohort of patients with myotonic dystrophy. Neurology. 1999;52:1658–62. [PubMed: 10331695]
  76. Matsumura T, Iwahashi H, Funahashi T, Takahashi MP, Saito T, Yasui K, Saito T, Iyama A, Toyooka K, Fujimura H, Shinno S. A cross-sectional study for glucose intolerance of myotonic dystrophy. J Neurol Sci. 2009;276:60–5. [PubMed: 18834994]
  77. Maurage CA, Udd B, Ruchoux MM, Vermersch P, Kalimo H, Krahe R, Delacourte A, Sergeant N. Similar brain tau pathology in DM2/PROMM and DM1/Steinert disease. Neurology. 2005;65:1636–8. [PubMed: 16301494]
  78. Meola G, Cardani R. Myotonic dystrophies: An update on clinical aspects, genetic, pathology, and molecular pathomechanisms. Biochim Biophys Acta. 2015;1852:594–606. [PubMed: 24882752]
  79. Minnerop M, Weber B, Schoene-Bake JC, Roeske S, Mirbach S, Anspach C, Schneider-Gold C, Betz RC, Helmstaedter C, Tittgemeyer M, Klockgether T, Kornblum C. The brain in myotonic dystrophy 1 and 2: evidence for a predominant white matter disease. Brain. 2011;134:3530–46. [PMC free article: PMC3235566] [PubMed: 22131273]
  80. Mladenovic J, Pekmezovic T, Todorovic S, Rakocevic-Stojanovic V, Savic D, Romac S, Apostolski S. Survival and mortality of myotonic dystrophy type 1 (Steinert's disease) in the population of Belgrade. Eur J Neurol. 2006;13:451–4. [PubMed: 16722967]
  81. Modoni A, Silvestri G, Pomponi MG, Mangiola F, Tonali PA, Marra C. Characterization of the pattern of cognitive impairment in myotonic dystrophy type 1. Arch Neurol. 2004;61:1943–7. [PubMed: 15596617]
  82. Modoni A, Silvestri G, Vita MG, Quaranta D, Tonali PA, Marra C. Cognitive impairment in myotonic dystrophy type 1 (DM1): a longitudinal follow-up study. J Neurol. 2008;255:1737–42. [PubMed: 18821050]
  83. Montella L, Caraglia M, Addeo R, Costanzo R, Faiola V, Abbruzzese A, Del Prete S. Atrial fibrillation following chemotherapy for stage IIIE diffuse large B-cell gastric lymphoma in a patient with myotonic dystrophy (Steinert's disease). Ann Hematol. 2005;84:192–3. [PubMed: 15042318]
  84. Mörner S, Lindqvist P, Mellberg C, Olofsson BO, Backman C, Henein M, Lundblad D, Forsberg H. Profound cardiac conduction delay predicts mortality in myotonic dystrophy type 1. J Intern Med. 2010;268:59–65. [PubMed: 20337852]
  85. Motlagh B, MacDonald JR, Tarnopolsky MA. Nutritional inadequacy in adults with muscular dystrophy. Muscle Nerve. 2005;31:713–8. [PubMed: 15786416]
  86. Moxley RT, Meola G. The myotonic dystrophies. In: The Molecular and Genetic Basis of Neurologic and Psychiatric Disease. Rosenberg RN, DiMauro S, Paulson HL, Ptacek L, Nestler EJ, eds. Philadelphia, PA: Wolters Kluwer; 2008:532-41.
  87. Nishi M, Itoh H, Tsubokawa T, Taniguchi T, Yamamoto K. Effective doses of vecuronium in a patient with myotonic dystrophy. Anaesthesia. 2004;59:1216–8. [PubMed: 15549982]
  88. Ørngreen MC, Arlien-Søborg P, Duno M, Hertz JM, Vissing J. Endocrine function in 97 patients with myotonic dystrophy type 1. J Neurol. 2012;259:912–20. [PubMed: 22349862]
  89. Oyamada R, Hayashi M, Katoh Y, Tsuchiya K, Mizutani T, Tominaga I, Kashima H. Neurofibrillary tangles and deposition of oxidative products in the brain in cases of myotonic dystrophy. Neuropathology. 2006;26:107–14. [PubMed: 16708543]
  90. Parisi M, Galderisi M, Sidiropulos M, Fiorillo C, Lanzillo R, D'Errico A, Grieco M, Innelli P, Santoro L, de Divitiis O. Early detection of biventricular involvement in myotonic dystrophy by tissue Doppler. Int J Cardiol. 2007;118:227–32. [PubMed: 17045670]
  91. Passeri E, Bugiardini E, Sansone VA, Valaperta R, Costa E, Ambrosi B, Meola G, Corbetta S. Vitamin D, parathyroid hormone and muscle impairment in myotonic dystrophies. J Neurol Sci. 2013;331:132–5. [PubMed: 23809192]
  92. Peric S, Stojanovic VR, Nikolic A, Kacar A, Basta I, Pavlovic S, Lavrnic D. Peripheral neuropathy in patients with myotonic dystrophy type 1. Neurol Res. 2013;35:331–5. [PubMed: 23336676]
  93. Peric S, Sreckov M, Basta I, Lavrnic D, Vujnic M, Marjanovic I, Rakocevic Stojanovic V. Dependent and paranoid personality patterns in myotonic dystrophy type 1. Acta Neurol Scand. 2014;129:219–25. [PubMed: 24032453]
  94. Petri H, Vissing J, Witting N, Bundgaard H, Køber L. Cardiac manifestations of myotonic dystrophy type 1. Int J Cardiol. 2012;160:82–8. [PubMed: 21917328]
  95. Pincherle A, Patruno V, Raimondi P, Moretti S, Dominese A, Martinelli-Boneschi F, Pasanisi MB, Canioni E, Salerno F, Deleo F, Spreafico R, Mantegazza R, Villani F, Morandi L. Sleep breathing disorders in 40 Italian patients with Myotonic dystrophy type 1. Neuromuscul Disord. 2012;22:219–24. [PubMed: 22137426]
  96. Pratte A, Prévost C, Puymirat J, Mathieu J. Anticipation in myotonic dystrophy type 1 parents with small CTG expansions. Am J Med Genet A. 2015;167A:708–14. [PubMed: 25712547]
  97. Prior TW. American College of Medical Genetics (ACMG) Laboratory Quality Assurance Committee - Technical standards and guidelines for myotonic dystrophy type 1 testing. Genet Med. 2009;11:552–5. [PubMed: 19546810]
  98. Rakocević-Stojanović V, Savić D, Pavlović S, Lavrnić D, Stević Z, Basta I, Romac S, Apostolski S. Intergenerational changes of CTG repeat depending on the sex of the transmitting parent in myotonic dystrophy type 1. Eur J Neurol. 2005;12:236–7. [PubMed: 15693817]
  99. Ranum LP, Day JW. Myotonic dystrophy: RNA pathogenesis comes into focus. Am J Hum Genet. 2004;74:793–804. [PMC free article: PMC1181975] [PubMed: 15065017]
  100. Redman JB, Fenwick RG Jr, Fu YH, Pizzuti A, Caskey CT. Relationship between parental trinucleotide GCT repeat length and severity of myotonic dystrophy in offspring. JAMA. 1993;269:1960–5. [PubMed: 8464127]
  101. Ricker K, Grimm T, Koch MC, Schneider C, Kress W, Reimers CD, Schulte-Mattler W, Mueller-Myhsok B, Toyka KV, Mueller CR. Linkage of proximal myotonic myopathy to chromosome 3q. Neurology. 1999;52:170–1. [PubMed: 9921867]
  102. Romeo V, Pegoraro E, Ferrati C, Squarzanti F, Sorarù G, Palmieri A, Zucchetta P, Antunovic L, Bonifazi E, Novelli G, Trevisan CP, Ermani M, Manara R, Angelini C. Brain involvement in myotonic dystrophies: neuroimaging and neuropsychological comparative study in DM1 and DM2. J Neurol. 2010;257:1246–55. [PubMed: 20221771]
  103. Rönnblom A, Forsberg H, Danielsson A. Gastrointestinal symptoms in myotonic dystrophy. Scand J Gastroenterol. 1996;31:654–7. [PubMed: 8819213]
  104. Roses AD. Myotonic dystrophy. In: Rosenberg RN, Prusiner SB, Dimauro S, Barchi RL, eds. The Molecular and Genetic Basis of Neurological Disease. 2 ed. Stoneham, MA: Butterworth-Heinemann; 1997.
  105. Rubinsztein JS, Rubinsztein DC, Goodburn S, Holland AJ. Apathy and hypersomnia are common features of myotonic dystrophy. J Neurol Neurosurg Psychiatry. 1998;64:510–5. [PMC free article: PMC2170039] [PubMed: 9576545]
  106. Sá MI, Cabral S, Costa PD, Coelho T, Freitas M, Gomes JL. Ambulatory electrocardiographic monitoring in type 1 myotonic dystrophy. Rev Port Cardiol. 2007;2007;26:745–53. [PubMed: 17939583]
  107. Sansone V, Gandossini S, Cotelli M, Calabria M, Zanetti O, Meola G. Cognitive impairment in adult myotonic dystrophies: a longitudinal study. Neurol Sci. 2007;28:9–15. [PubMed: 17385090]
  108. Savkur RS, Philips AV, Cooper TA. Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet. 2001;29:40–7. [PubMed: 11528389]
  109. Sistiaga A, Urreta I, Jodar M, Cobo AM, Emparanza J, Otaegui D, Poza JJ, Merino JJ, Imaz H, Martí-Massó JF, López de Munain A. Cognitive/personality pattern and triplet expansion size in adult myotonic dystrophy type 1 (DM1): CTG repeats, cognition and personality in DM1. Psychol Med. 2010;40:487–95. [PubMed: 19627641]
  110. Sovari AA, Bodine CK, Farokhi F. Cardiovascular manifestations of myotonic dystrophy-1. Cardiol Rev. 2007;15:191–4. [PubMed: 17575483]
  111. Spranger M, Spranger S, Tischendorf M, Meinck HM, Cremer M. Myotonic dystrophy. The role of large triplet repeat length in the development of mental retardation. Arch Neurol. 1997;54:251–4. [PubMed: 9074392]
  112. Takado Y, Terajima K, Ohkubo M, Okamoto K, Shimohata T, Nishizawa M, Igarashi H, Nakada T. Diffuse brain abnormalities in myotonic dystrophy type 1 detected by 3.0 T proton magnetic resonance spectroscopy. Eur Neurol. 2015;73:247–56. [PubMed: 25824277]
  113. Talbot K, Stradling J, Crosby J, Hilton-Jones D. Reduction in excess daytime sleepiness by modafinil in patients with myotonic dystrophy. Neuromuscul Disord. 2003;13:357–64. [PubMed: 12798791]
  114. Theadom A, Rodrigues M, Roxburgh R, Balalla S, Higgins C, Bhattacharjee R, Jones K, Krishnamurthi R, Feigin V. Prevalence of muscular dystrophies: a systematic literature review. Neuroepidemiology. 2014;43:259–68. [PubMed: 25532075]
  115. Thornton CA. Myotonic dystrophy. Neurol Clin. 2014;32:705–19. [PMC free article: PMC4105852] [PubMed: 25037086]
  116. Turkbey EB, Gai N, Lima JA, van der Geest RJ, Wagner KR, Tomaselli GF, Bluemke DA, Nazarian S. Assessment of cardiac involvement in myotonic muscular dystrophy by T1 mapping on magnetic resonance imaging. Heart Rhythm. 2012;9:1691–7. [PMC free article: PMC3459147] [PubMed: 22710483]
  117. Turner C, Hilton-Jones D. The myotonic dystrophies: diagnosis and management. J Neurol Neurosurg Psychiatry. 2010;81:358–67. [PubMed: 20176601]
  118. Turner C, Hilton-Jones D. Myotonic dystrophy: diagnosis, management and new therapies. Curr Opin Neurol. 2014;27:599–606. [PubMed: 25121518]
  119. Udd B, Krahe R. The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol. 2012;11:891–905. [PubMed: 22995693]
  120. Udd B, Meola G, Krahe R, Thornton C, Ranum LP, Bassez G, Kress W, Schoser B, Moxley R. 140th ENMC International Workshop: Myotonic Dystrophy DM2/PROMM and other myotonic dystrophies with guidelines on management. Neuromuscul Disord. 2006;16:403–13. [PubMed: 16684600]
  121. Umemoto G, Nakamura H, Oya Y, Kikuta T. Masticatory dysfunction in patients with myotonic dystrophy (type 1): a 5-year follow-up. Spec Care Dentist. 2009;29:210–4. [PubMed: 19740152]
  122. van der Kooi EL, Lindeman E, Riphagen I. Strength training and aerobic exercise training for muscle disease. Cochrane Database Syst Rev. 2005:CD003907. [PubMed: 15674918]
  123. Verpoest W, De Rademaeker M, Sermon K, De Rycke M, Seneca S, Papanikolaou E, Spits C, Van Landuyt L, Van der Elst J, Haentjens P, Devroey P, Liebaers I. Real and expected delivery rates of patients with myotonic dystrophy undergoing intracytoplasmic sperm injection and preimplantation genetic diagnosis. Hum Reprod. 2008;23:1654–60. [PubMed: 18408243]
  124. Verpoest W, Seneca S, De Rademaeker M, Sermon K, De Rycke M, De Vos M, Haentjens P, Devroey P, Liebaers I. The reproductive outcome of female patients with myotonic dystrophy type 1 (DM1) undergoing PGD is not affected by the size of the expanded CTG repeat tract. J Assist Reprod Genet. 2010;27:327–33. [PMC free article: PMC2914592] [PubMed: 20221684]
  125. Veyckemans F, Scholtes JL. Myotonic dystrophies type 1 and 2: anesthetic care. Paediatr Anaesth. 2013;23:794–803. [PubMed: 23384336]
  126. Wahbi K, Meune C, Porcher R, Bécane HM, Lazarus A, Laforêt P, Stojkovic T, Béhin A, Radvanyi-Hoffmann H, Eymard B, Duboc D. Electrophysiological study with prophylactic pacing and survival in adults with myotonic dystrophy and conduction system disease. JAMA. 2012;307:1292–301. [PubMed: 22453570]
  127. Wheeler TM, Thornton CA. Myotonic dystrophy: RNA-mediated muscle disease. Curr Opin Neurol. 2007;20:572–6. [PubMed: 17885447]
  128. Whittaker RG, Ferenczi E, Hilton-Jones D. Myotonic dystrophy: practical issues relating to assessment of strength. J Neurol Neurosurg Psychiatry. 2006;77:1282–3. [PMC free article: PMC2077393] [PubMed: 17043296]
  129. Win AK, Perattur PG, Pulido JS, Pulido CM, Lindor NM. Increased cancer risks in myotonic dystrophy. Mayo Clin Proc. 2012;87:130–5. [PMC free article: PMC3498332] [PubMed: 22237010]
  130. Winblad S, Lindberg C, Hansen S. Temperament and character in patients with classical myotonic dystrophy type 1 (DM-1). Neuromuscul Disord. 2005;15:287–92. [PubMed: 15792867]
  131. Wintzen AR, Lammers GJ, van Dijk JG. Does modafinil enhance activity of patients with myotonic dystrophy?: a double-blind placebo-controlled crossover study. J Neurol. 2007;254:26–8. [PMC free article: PMC1915648] [PubMed: 17285226]
  132. Wozniak JR, Mueller BA, Bell CJ, Muetzel RL, Lim KO, Day JW. Diffusion tensor imaging reveals widespread white matter abnormalities in children and adolescents with myotonic dystrophy type 1. J Neurol. 2013;260:1122–31. [PMC free article: PMC3609908] [PubMed: 23192171]
  133. Yotova V, Labuda D, Zietkiewicz E, Gehl D, Lovell A, Lefebvre JF, Bourgeois S, Lemieux-Blanchard E, Labuda M, Vezina H, Houde L, Tremblay M, Toupance B, Heyer E, Hudson TJ, Laberge C. Anatomy of a founder effect: myotonic dystrophy in Northeastern Quebec. Hum Genet. 2005;117:177–87. [PubMed: 15883838]
  134. Zaki M, Boyd PA, Impey L, Roberts A, Chamberlain P. Congenital myotonic dystrophy: prenatal ultrasound findings and pregnancy outcome. Ultrasound Obstet Gynecol. 2007;29:284–8. [PubMed: 17238150]
  135. Zampetti A, Silvestri G, Manco S, Khamis K, Masciullo M, Bianchi ML, Damiani A, Santoro M, Linder D, Bewley A, Feliciani C. Dysplastic nevi, cutaneous melanoma, and other skin neoplasms in patients with myotonic dystrophy type 1: a cross-sectional study. J Am Acad Dermatol. 2015;72:85–91. [PubMed: 25440959]
  136. Zeesman S, Carson N, Whelan DT. Paternal transmission of the congenital form of myotonic dystrophy type 1: a new case and review of the literature. Am J Med Genet. 2002;107:222–6. [PubMed: 11807903]

Suggested Reading

  1. Dubowitz Z. Muscle Disorders in Childhood. 2 ed. London, UK: WB Saunders; 1995.
  2. Groh WJ, Groh MR, Saha C, Kincaid JC, Simmons Z, Ciafaloni E, Pourmand R, Otten RF, Bhakta D, Nair GV, Marashdeh MM, Zipes DP, Pascuzzi RM. Electrocardiographic abnormalities and sudden death in myotonic dystrophy type 1. N Engl J Med. 2008;358:2688–97. [PubMed: 18565861]
  3. Hamshere M, Newman E, Alwazzan M, Brook JD. Myotonic dystrophy. In: Rubinsztein DC, Hayden MR, eds. Analysis of Triplet Repeat Disorders. Oxford, UK: BIOS Scientific Publishers Ltd; 1998:61-84.
  4. Harper PS, Johnson K. Myotonic dystrophy. In: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G, eds. The Online Metabolic and Molecular Bases of Inherited Disease (OMMBID). Chap 217. New York, NY: McGraw-Hill. Available online. 2014. Accessed 10-22-15.
  5. Mankodi A, Urbinati CR, Yuan QP, Moxley RT, Sansone V, Krym M, Henderson D, Schalling M, Swanson MS, Thornton CA. Muscleblind localizes to nuclear foci of aberrant RNA in myotonic dystrophy types 1 and 2. Hum Mol Genet. 2001;10:2165–70. [PubMed: 11590133]
  6. Ranum LP, Cooper TA. RNA-mediated neuromuscular disorders. Annu Rev Neurosci. 2006;29:259–77. [PubMed: 16776586]
  7. Roses AD, Adams C. Myotonic dystrophy. In: Pulst SM, ed. Neurogenetics. New York, NY: Oxford University Press; 1999:117-30.

Chapter Notes

Acknowledgments

NIH CAP Award (3 MO1 RR00425-2856)

Author History

Cameron Adams, MD; Cedars-Sinai Medical Center (1999-2004)
Thomas D Bird, MD (2004-present)

Revision History

  • 22 October 2015 (tb) Revision: clarification in Genetic Counseling, Offspring of a proband
  • 10 September 2015 (me) Comprehensive update posted live
  • 16 May 2013 (me) Comprehensive update posted live
  • 8 February 2011 (me) Comprehensive update posted live
  • 15 November 2007 (me) Comprehensive update posted to live Web site
  • 22 November 2005 (tb) Revision: reference added to Molecular Genetic Testing
  • 9 August 2004 (tb) Revision
  • 14 August 2001 (tb) Revision by Associate Editor TD Bird, MD
  • 17 September 1999 (me) Review posted to live Web site
  • 31 December 1998 (ca) Original submission
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