Myotonic dystrophies are multisystemic diseases with autosomal dominant inheritance pattern that represent the most common muscular dystrophies in adults. The prevalence for myotonic dystrophy type 1 (DM1) is estimated at 1:8,000. Onset of symptoms, such as myotonia characterized by delayed relaxation of a tense muscle, is most often observed in early adulthood. In addition, muscle weakness and fatigue occur, as well as dysphagia, an elongated face with poor facial expression, cataract, diabetes mellitus, cardiac arrythmias; in males, early development of a bald forehead and testicular atrophy. The clinical presentation of DM1 is categorized into four partially overlapping phenotypes: asymptomatic, mild, classic, and neonatal. The congenital form is characterized by pronounced muscle hypotonia, often with clubfoot formation, usually associated with respiratory insufficiency and weakness in drinking. Psychomotor development is often delayed. This type occurs predominantly when the disease is passed down from the mother and only in DM1.
DM1 is caused by a CTG repeat expansion in the non-translated 3′ region of the DMPK gene on chromosome 19, which encodes a protein kinase. DM2 (Proximal myotonic myopathy=PROMM-OMIM-No: 602688), which is important for differential diagnosis, is caused by expansion of a CCTG repeat in intron 1 of the ZNF9 gene on chromosome 3. The phenomenon of anticipation – meaning a decrease in the age of onset of the disease and/or an increase in the severity of symptoms from one generation to the next – is particularly pronounced in DM1. Healthy individuals have 5-36 CTG repeats in the DMPK gene, DM patients have up to approx. 1,000. Children with the congenital type have more than 1,000 repeats.
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