Myotonic Dystrophy (DM)

Types of Myotonic Dystrophy

Myotonic dystrophy (DM) includes two major types — DM1 and DM2 — both caused by genetic defects. They result in multisystem disorders characterized by skeletal muscle weakness and myotonia (difficulty relaxing muscles after use), cardiac abnormalities, cataracts, and other abnormalities.

DM1, the most common type, results from an abnormal DNA expansion in the DMPK gene on chromosome 19. DM2 arises from an abnormal expansion of DNA in the ZNF9 gene on chromosome 3. Within DM1 are additional subtypes, depending on a person’s age at onset of symptoms. The age of onset is roughly correlated with the size of the disease’s associated DNA expansion; larger expansions associated with earlier disease onset.

DM1 subtypes include:

• Congenital-onset DM1 — may present before birth with decreased fetal movement and is characterized by severe muscle weakness, profound hypotonia, poor feeding, joint contractures, cognitive impairment, respiratory failure, and other developmental abnormalities
• Childhood- or juvenile-onset DM1 — begins during childhood (after birth but before adolescence) and is characterized by cognitive and behavioral symptoms, muscle weakness, myotonia, anxiety, mood disorders, attentional deficits, and other symptoms. Some patients may have arrhythmias when playing sports, and in 10% of patients, cardiomyopathy and heart failure might be diagnosed 
• Adult-onset (classic) DM1 — begins in adolescence or early adulthood and is characterized by slowly progressive weakness, myotonia, cardiac abnormalities, respiratory weakness, cataracts, and, sometimes, mild to moderate cognitive difficulties
• Mild DM1 – usually appears in 20- to 70-year-old patients, typically after age 40. This mild  form of DM1 is characterized by mild weakness, myotonia, and cataracts

DM2 — sometimes called PROMM (proximal myotonic myopathy) — has not been seen in a congenital-onset form and rarely begins in childhood. Therefore, it is not described in subtypes. DM2 tends to involve the proximal muscles (close to the center of the body) rather than the distal muscles (far from the center of the body) that are the first to be affected in DM1. In general, DM2 is a less severe disease than classic DM1. However, it may affect walking ability earlier than DM1 because it causes early weakening of the hip muscles. DM2 is rare compared to DM1, except in people of German descent.

For more, see Causes/Inheritance.

Below is a general comparison of the major features of DM1 and DM2.

Comparison of DM1 and DM2
Feature	DM1	DM2
Age of onset	Birth to adulthood	10 to 60 years
Facial weakness	Prominent	Mild
Neck muscle weakness	Common, early	Common, early, less severe
Hip and thigh weakness	As a result of a gradual progression	Early, presenting feature of DM2 1, 2
Distal muscle weakness	Prominent	Proximal weakness
Muscle pain	Common symptom	Induced by exercise and temperature change
Myotonia	Occurs	Occurs
Early cataracts (clouding of the lens in the eyes)	Occurs	Occurs
Cardiac rhythm abnormalities	Common	Variable
Hypersomnia excessive daytime sleepiness (EDS)	Common	Less prevalent and less severe3
Cognitive impairment	Occurs often; can be mild to severe	Can occur, generally mild, and intellectual disability is rare
Respiratory abnormalities	Common, particularly sleep-disordered breathing and inadequate breathing	Rare
Gastrointestinal disturbances	Difficulty to swallow, abdominal pain, diarrhea, constipation, irritable bowel syndrome, bloating, gallstones can occur	Mild difficulty to swallow solid food, abdominal pain, and constipation4, 5
Uterine dysfunction during labor and delivery	Can occur	Not common
High blood sugar because of insulin resistance, diabetes	Can occur	Can occur; prevalence of diabetes is greater than in DM1

References

1. Day, J. W. et al. Myotonic dystrophy type 2: Molecular, diagnostic and clinical spectrum. Neurology (2003). doi:10.1212/01.WNL.0000054481.84978.F9
2. Papadimas, G. K. et al. Phenotypic variability and molecular genetics in proximal myotonic myopathy. Muscle and Nerve (2015). doi:10.1002/mus.24440
3. Tieleman, A. A. et al. Poor sleep quality and fatigue but no excessive daytime sleepiness in myotonic dystrophy type 2. J. Neurol. Neurosurg. Psychiatry (2010). doi:10.1136/jnnp.2009.192591
4. Tieleman, A. A. et al. Gastrointestinal involvement is frequent in Myotonic Dystrophy type 2. Neuromuscul. Disord. (2008). doi:10.1016/j.nmd.2008.05.010
5. Tieleman, A. A. et al. Dysphagia is present but mild in myotonic dystrophy type 2. Neuromuscul. Disord. (2009). doi:10.1016/j.nmd.2008.12.002