Anticipation tends to be less severe than in cases of maternal inheritance.The RNA from the expanded trinucleotide repeat region forms intranucleoplasmic hairpin loops due to the extensive hydrogen bonding between C-G base pairs, and it has been demonstrated that these sequester the splicing regulator MBNL1 to form distinctive foci.A severe form of DM1, congenital myotonic dystrophy, may appear in newborns of mothers who have DM. Congenital myotonic dystrophy can also be inherited via the paternal gene, although it is said to be relatively rare. Congenital means that the condition is present from birth. DM2
The microsatellite expansion responsible for DM2 is of cytosine-cytosine-thymine-guanine (CCTG) repeats, classifying it as a tetranucleotide repeat disorder. This expansion occurs in the first intron CNBP gene on chromosome 3.The repeat expansion for DM2 is much larger than for DM1, ranging from 75 to over 11,000 repeats. Like DM1, the size of the microsatellite repeat array lengthens from generation to generation. Unlike DM1, anticipation does not result, as the degree of repeat expansion beyond 75 repeats does not affect the age of onset or disease severity.The repeat expansion produces an RNA transcript that binds to RNA-binding proteins such as MBNL1, as in DM1. Also, repeat expansion likely reduces expression of CNBP, loss of which causes muscle toxicity. Pathophysiology
Molecular
Mutations of DM1 and DM2 cause production of RNA that sequesters RNA-binding proteins, causing dysregulated RNA splicing. This dysregulated RNA splicing is particularly toxic to skeletal, cardiac, and smooth muscle. One example in DM1 involves the chloride channel ClC-1.
Myotonic dystrophy (DM) is a type of muscular dystrophy, a group of genetic disorders that cause progressive muscle loss and weakness. In DM, muscles are often unable to relax after contraction. Other manifestations may include cataracts, intellectual disability and heart conduction problems. In men, there may be early balding and an inability to have children. While myotonic dystrophy can occur at any age, onset is typically in the 20s and 30s.Myotonic dystrophy is caused by a genetic mutation in one of two genes. Mutation of the DMPK gene causes myotonic dystrophy type 1 (DM1). Mutation of CNBP gene causes type 2 (DM2). DM is typically inherited from a persons parents, following an autosomal dominant inheritance pattern, and it generally worsens with each generation. A type of DM1 may be apparent at birth. DM2 is generally milder. Diagnosis is confirmed by genetic testing.There is no cure. Treatments may include braces or wheelchairs, pacemakers and non-invasive positive pressure ventilation. The medications mexiletine or carbamazepine can help relax muscles. Pain, if it occurs, may be treated with tricyclic antidepressants and nonsteroidal anti-inflammatory drugs (NSAIDs).Myotonic dystrophy affects more than 1 in 8,000 people worldwide. It is the most common form of muscular dystrophy that begins in adulthood. It was first described in 1909, with the underlying cause of type 1 determined in 1992. Signs and symptoms
DM causes muscle weakness, early onset of cataracts, and myotonia, which is delayed relaxation of muscles after contraction.