The reference OMIM entry for this protein is 160900

Myotonic dystrophy 1; dm1
Dystrophia myotonica 1
Dystrophia myotonica; dm
Steinert disease

A number sign (#) is used with this entry because myotonic dystrophy-1 (DM1) is caused by a heterozygous trinucleotide repeat expansion (CTG)n in the 3-prime untranslated region of the dystrophia myotonica protein kinase gene (DMPK; 605377) on chromosome 19q13. A repeat length exceeding 50 CTG repeats is pathogenic (Musova et al., 2009).

DESCRIPTION

Myotonic dystrophy is an autosomal dominant disorder characterized mainly by myotonia, muscular dystrophy, cataracts, hypogonadism, frontal balding, and ECG changes. The genetic defect in DM1 results from an amplified trinucleotide repeat in the 3-prime untranslated region of a protein kinase gene. Disease severity varies with the number of repeats: normal individuals have 5 to 37 repeats, mildly affected persons have 50 to 150 repeats, patients with classic DM have 100 to 1,000 repeats, and those with congenital onset can have more than 2,000 repeats. The disorder shows genetic anticipation, with expansion of the repeat number dependent on the sex of the transmitting parent. Alleles of 40 to 80 repeats are usually expanded when transmitted by males, whereas only alleles longer than 80 repeats tend to expand in maternal transmissions. Repeat contraction events occur 4.2 to 6.4% of the time (Musova et al., 2009). - Genetic Heterogeneity of Myotonic Dystrophy See also myotonic dystrophy-2 (DM2; 602668), which is caused by mutation in the ZNF9 gene (116955) on chromosome 3q.

CLINICAL FEATURES

- ADULT-ONSET MYOTONIC DYSTROPHY In adult-onset DM1, symptoms typically become evident in middle life, but signs can be detectable in the second decade. Bundey et al. (1970) found that the most useful method for identifying subclinical cases is slit-lamp examination for lens changes, followed by electromyography for myotonic discharges, and then by measurement of immunoglobulins. Harper (1989) provided a monograph on myotonic dystrophy that has been updated regularly. Unlike the other muscular dystrophies, DM initially involves the distal muscles of the extremities and only later affects the proximal musculature. In addition, there is early involvement of the muscles of the head and neck. Involvement of the extraocular muscles produces ptosis, weakness of eyelid closure, and limitation of extraocular movements. Atrophy of masseters, sternocleidomastoids, and the temporalis muscle produces a characteristic haggard appearance. Bosma and Brodie (1969) demonstrated both myotonia and weakness in patients with swallowing and speech disability. Myotonia, delayed muscular relaxation following contraction, is most frequently apparent in the tongue, forearm, and hand. Myotonia is rarely as severe as in myotonia congenita and tends to be less apparent as weakness progresses. Many of the muscle biopsy changes are nonspecific. Most commonly there are central nuclei and ring fibers. Necrosis, regeneration, and increase of collagen are never as severe as in Duchenne muscular dystrophy. In 70% of patients there is hypotrophy of type I muscle fibers; less commonly there are markedly atrophic fibers (Casanova and Jerusalem, 1979). In many cases there are target fibers, suggesting neurogenic dysfunction, but intramuscular nerves appear histologically normal (Drachman and Fambrough, 1976). Ultrastructural studies show dilatation of T tubules or sarcoplasmic reticulum, whose contents may be unusually dense (Fardeau et al., 1965). In some cases the surface membrane may be irregular, with reduplication of b ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 160900 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).