DM1 - Myotonic Dystrophy

DM1 is caused by expansion of an unstable trinucleotide repeat (CTG) in the 3’ untranslated region of the DMPK1 gene (Myotonic Dystrophy protein kinase). DMPK transcripts bearing a long (CUG)n tract can form hairpin-like structures that bind proteins of the muscleblind family and subsequently aggregate in ribonuclear foci in the nucleus. Since muscleblind proteins are splicing factors, their depletion results in a dramatic rearrangement in splicing of other transcripts, and thus non-functional proteins. Using RNA-modulating therapeutics, cellular production of aberrantly expanded DMPK mRNA may be prevented, and/or degradation of these toxic transcripts induced.

Type 1 Myotonic Dystrophy is caused by toxicity of a noncoding (CUG)n tract in DMPK transcripts. The expanded (CUG)n segment is responsible for entrapment of muscleblind (Mbnl) splicing factors in ribonuclear aggregates and stabilized expression of splicing factor CUGBP1. These RNA gain-of-function effects are implicated in aberrant pre-mRNA splicing observed in DM1 patients and probably other pathogenic phenomena of the disease.

Genetic counseling is maybe delicate for Myotonic Dystrophy because of the great variability of clinical expression, both within and between families. Prenatal diagnosis is proposed especially for maternal transmission because of the severity of the possible neonatal forms. Management ideally includes multidisciplinary annual follow-up.

Disease course is usually slowly progressive but rapid deterioration may sometimes be observed. Life expectancy is reduced by the increased mortality associated with the pulmonary and cardiac complications. Treatment is symptomatic. That is, problems associated with Myotonic Dystrophy are treated individually. For example, surgery is available for correction of cataracts. Medication may be prescribed to counter the effects of myotonia. Heart problems will be treated by a heart specialist depending on what symptoms are experienced. Children with developmental delays can be assisted by speech therapy and a modified school environment. Remaining as active as possible is recommended for everyone with Myotonic Dystrophy. Today no effective cure is available for DM1.