Myotonic Dystrophy Foundation

Working Together Toward a Cure

Myotonic dystrophy (DM) is a progressive genetic disorder that affects an estimated 1 in 8000 people. However, estimates of prevalence are based on studies of a relatively small number of cases and it is suspected that the prevalence may be much higher. One of the nine muscular dystrophies, myotonic dystrophy is the most common form of muscular dystrophy with onset in adult life and one of the most common forms of childhood-onset. However, classifying myotonic dystrophy as a muscle disease is misleading - myotonic dystrophy is considered the most variable neuromuscular disorder in terms of severity, age at onset, and different body systems affected.

Clinical Presentation

Affected individuals vary greatly in terms of their age at onset of symptoms, the range of systems affected,and the severity of the symptoms experienced. Signficant differences are seen between members of the same family and between individuals with identical mutations.  Discordant symptoms have even been seen with monozygotic twins, suggesting that post-zygotic changes and other factors play a key role in disease manifestation.

Myotonic dystrophy can present with highly variable issues such as reduced cognitive function, vision impairment, gastrointestinal disturbances, endocrine deficiency, fertility issues, cardiovascular dysfunction, or respiratory insufificiency in addition to muscle complaints. Because of the range of systems affected, affected individuals may see multiple specialists who are unaware of the full spectrum of issues experienced by their patient. This variability presents unique challenges in both the diagnosis and management of the disease. Multi-disciplinary teams are often required to provide comprehensive, coordinated clinical care. 

No cure exists for myotonic dystrophy, nor are there any treatments that slow the progression of the disease. Disease management is symptomatically-driven and varies greatly depending on the form of myotonic dystrophy seen. Childhood onset and congenital myotonic dystrophy present significantly differently from adult onset forms of myotonic dystrophy and require special management. Pregnancy in affected mothers poses serious complications for both the mother and the newborn, often requiring intensive intervention.

Further detail on the symptoms, diagnosis and management of each system affected by myotonic dystrophy is available by clicking here.

Genetic Origins 

Myotonic dystrophy is a triplet repeat disease caused by an autosomal dominant mutation.

Myotonic dystrophy type 1 (DM1), also known as Steinert's disease, has three subtypes that vary based on age at onset: a severe congenital form with life-threatening issues at birth, a childhood onset form which typically first presents with mental retardation and learning disabilitiies, and an adult onset form characterized by distal muscle weakness, atrophy, and myotonia. DM1 is caused by an expanded and unstable (CTG)n trinucleotide repeat, located in the 3’ untranslated region of the dystrophia myotonica-protein kinase (DMPK) gene on chromosome 19.

Myotonic dystrophy type 2 (DM2), also known as proximal myotonic myopathy (PROMM), is a milder form of myotonic dystrophy where transient muscle pain is the most common complaint. Only adult-onset forms of DM2 have been recognized. DM2 is caused by a mutation in the first intron of the zinc finger 9 (Cnbp also known as Znf9) gene on chromosome 3.

Additional forms (DM3, DM4) have been suggested, as a small number of individuals have been seen who have the characteristic symptoms of myotonic dystrophy, but who do not have the genetic mutations which cause these disroders. Considerable debate exists as to whether these individuals truly represent a new form of myotonic dystrophy or whether they simply present unique diagnostic challenges.

Further detail on the genetic cause and molecular basis of myotonic dystrophy is available by clicking here.