Myotonic dystrophy

Myotonic dystrophy (DM) is the most common form of adult-onset muscular dystrophy and belongs to a group of disorders characterized by myotonia (delayed relaxation of muscles after contraction) and progressive muscle weakness and wasting. There are two major forms: myotonic dystrophy type 1 (DM1, also known as Steinert disease), caused by a CTG trinucleotide repeat expansion in the DMPK gene on chromosome 19q13.3, and myotonic dystrophy type 2 (DM2, also known as proximal myotonic myopathy or PROMM), caused by a CCTG tetranucleotide repeat expansion in the CNBP (ZNF9) gene on chromosome 3q21.3. Both forms are inherited in an autosomal dominant pattern and exhibit anticipation, meaning symptoms may appear earlier and become more severe in successive generations, particularly in DM1. Myotonic dystrophy is a multisystem disorder affecting far more than just skeletal muscle. Key clinical features include progressive distal muscle weakness and myotonia (more prominent in DM1), cataracts (posterior subcapsular iridescent opacities), cardiac conduction defects and arrhythmias, endocrine abnormalities including insulin resistance and hypogonadism, excessive daytime sleepiness, cognitive impairment, and gastrointestinal dysfunction. DM1 has a congenital form presenting at birth with severe hypotonia, respiratory failure, and intellectual disability, as well as a childhood-onset form. DM2 tends to present in adulthood with more proximal muscle weakness and generally follows a milder course than DM1. There is currently no cure or disease-modifying therapy for myotonic dystrophy. Management is symptomatic and multidisciplinary, involving regular cardiac monitoring (ECG, Holter monitoring) with pacemaker or defibrillator implantation when indicated, treatment of myotonia with medications such as mexiletine, management of cataracts with surgical intervention, respiratory support including non-invasive ventilation when needed, and endocrine management. Patients require careful anesthetic management due to heightened sensitivity to sedatives and increased risk of cardiac and respiratory complications. Genetic counseling is essential given the autosomal dominant inheritance and the phenomenon of anticipation. Several antisense oligonucleotide and gene-targeting therapies are under investigation in clinical trials.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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