Myotonic Dystrophy Type 1
Myotonic dystrophy type 1(DM1), also called Steinert disease, has a severe congenital form and a milder childhood-onset form.
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 permutations 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. Interestingly, paternal transmission of the condition is very uncommon, possibly due to selection pressures against sperm with expanded repeats, but anticipation tends to be more severe than in cases of maternal inheritance.