Clinical Pearls & Morning Reports
Published May 1, 2019
Myotonic dystrophy is a group of nucleotide repeat expansion diseases that are characterized by hyperexcitable muscle with impaired relaxation (myotonia). Read the Clinical Problem-Solving article here.
Q: What characterizes the two forms of myotonic dystrophy?
A: The two autosomal dominant forms are myotonic dystrophy type 1, which is caused by a CTG trinucleotide repeat expansion in the 3´ untranslated region of DMPK, and myotonic dystrophy type 2, which is caused by a CCTG tetranucleotide repeat expansion in intron 1 of the CCHC-type zinc finger, nucleic acid binding protein gene (CNBP, encoding zinc finger protein 9 [ZNF9]). In both diseases, RNA molecules with nucleotide repeat sequences disrupt normal mRNA splicing processes.
Q: How common is myotonic dystrophy?
A: Myotonic dystrophy occurs in nearly every ethnic group and is thought to be the most common inherited neuromuscular disease, with an estimated overall prevalence of 1 in 8000 persons. Type 1 is thought to be more common than type 2; however, the incidence and prevalence remain incompletely defined.
A: Symptoms associated with myotonic dystrophy type 1 correlate with the number of CTG repeat expansions. Phenotypes range from bulbar weakness and failure to thrive in babies with congenital disease (typically more than 1000 CTG repeats) to distal weakness, disabling myotonia, and cardiac arrhythmia in childhood-onset classic disease (typically in the range of 50 to 1000 CTG repeats) to early-onset cataracts, frontal balding, and subtle myotonia in the late-onset form (typically in the range of 50 to 100 CTG repeats). Persons with fewer than 50 CTG repeats are typically unaffected. Approximately 20% of patients with late-onset myotonic dystrophy type 1 do not have muscle weakness at presentation. Extraneurologic manifestations include cataracts (in approximately 75% of patients with late-onset myotonic dystrophy type 1), endocrine disorders (in 40%), and cardiac abnormalities, predominantly conduction disturbances (in 30%).
A: The average age of patients at diagnosis of myotonic dystrophy type 1 and type 2 is 26 years and 34 years, respectively. Delays in diagnosis are common; on average, the time from symptom onset to diagnosis is 7.3 years in patients with myotonic dystrophy type 1 and 14.4 years in patients with myotonic dystrophy type 2. Consensus treatment recommendations for myotonic dystrophy type 1 emphasize interdisciplinary care for its multiorgan manifestations. Myotonia treatments include sodium-channel–blocking class I antiarrhythmic and antiepileptic drugs, tricyclic antidepressants, and calcium-channel antagonists, but these medications have not been evaluated in large, randomized, controlled trials with clinically relevant outcome measures. Strength and skill training are the best-supported interventions to preserve function. Patients with late-onset myotonic dystrophy type 1 have normal life spans, whereas in the classic and congenital forms of myotonic dystrophy, cardiopulmonary complications reduce life expectancy. Treatments include an implantable cardioverter–defibrillator to prevent sudden cardiac death and noninvasive mechanical ventilation to reduce daytime fatigue.