page_title: Myotonic dystrophy
section_title: DM1
hierarchical_section_title: Myotonic dystrophy / Genetics / DM1
caption_attribution_description: English: Histopathology of Myotonic Dystrophy Type 2 (DM2, PROMM). Muscle biopsy showing mild myopathic changes and grouping of atrophic fast Fibres (Type 2, highlighted). Imunohistochemical staining for Type-1 ("slow") Myosin
context_page_description: Myotonic dystrophy is a long-term genetic disorder that affects muscle function. It is a type of muscular dystrophy. Symptoms include gradually worsening muscle loss and weakness. Muscles often contract and are unable to relax. Other symptoms may include cataracts, intellectual disability and heart conduction problems. In men, there may be early balding and an inability to have children.
  Myotonic dystrophy is an autosomal dominant disorder which is typically inherited from a person's parents. There are two main types: type 1, due to mutations in the DMPK gene, and type 2, due to mutations in the CNBP gene. The disorder generally worsens in 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 are occasionally helpful. Pain, if it occurs, may be treated with tricyclic antidepressants and nonsteroidal anti-inflammatory drugs.
  Myotonic dystrophy affects more than 1 in 8,000 people worldwide.
context_section_description: In DM1, the affected gene is called DMPK, which codes for myotonic dystrophy protein kinase, a protein expressed predominantly in skeletal muscle. The gene is located on the long arm of chromosome 19.
  In DM1, there is an expansion of the cytosine-thymine-guanine (CTG) triplet repeat in the DMPK gene. Between 5 and 37 repeats is considered normal, while individuals with between 38 and 49 repeats are considered to have a pre-mutation and are at risk of having children with further expanded repeats and, therefore, symptomatic disease. Individuals with greater than 50 repeats are almost invariably symptomatic, with some noted exceptions. Longer repeats are usually associated with earlier onset and more severe disease.
  DMPK alleles with greater than 37 repeats are unstable and additional trinucleotide repeats may be inserted during cell division in mitosis and meiosis. Consequently, the children of individuals with premutations or mutations inherit DMPK alleles which are longer than their parents and therefore are more likely to be affected or display an earlier onset and greater severity of the condition, a phenomenon known as anticipation. Repeat expansion is generally considered to be a consequence of the incorporation of additional bases as a result of strand slippage during either DNA replication or DNA repair synthesis.  Misalignments occurring during homologous recombinational repair, double-strand break repair or during other DNA repair processes likely contribute to trinucleotide repeat expansions in DM1. Paternal transmission of the congenital form is uncommon (13%), possibly due to selection pressures against sperm with expanded repeats, but juvenile or adult onset is equally transmitted from either parent. 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.
caption: Histopathology of DM2. Muscle biopsy showing mild myopathic changes and grouping of atrophic fast fibres (type 2, highlighted). Immunohistochemical staining for type-1 ("slow") myosin
exif: {"Image Orientation": "Horizontal (normal)", "Image XResolution": "600", "Image YResolution": "600", "Image ResolutionUnit": "Pixels/Inch", "Image Software": "Adobe Photoshop CS Windows", "Image DateTime": "2010:02:24 08:49:20", "Image Artist": "Admin", "Image ExifOffset": "180", "Thumbnail Compression": "JPEG (old-style)", "Thumbnail XResolution": "72", "Thumbnail YResolution": "72", "Thumbnail ResolutionUnit": "Pixels/Inch", "Thumbnail JPEGInterchangeFormat": "318", "Thumbnail JPEGInterchangeFormatLength": "8202", "EXIF ColorSpace": "sRGB", "EXIF ExifImageWidth": "2269", "EXIF ExifImageLength": "1944"}