Myotone Dystrophien: Klinik, Pathogenese, Diagnostik und Therapie

Abstract

The autosomal-dominant myotonic dystrophies dystrophia myotonica type-1 (DM1, Curschmann-Steinert disease) and dystrophia myotonica type-2 (DM2, proximal myotonic myopathy (PROMM)), are, contrary to the non-dystrophic myotonias, progressive multisystem disorders. DM1 and DM2 are the most frequent of the muscular dystrophies. In both diseases the skeletal muscle is the most severely affected organ (weakness, wasting, myotonia, myalgia). Additionally, they manifest in the eye, heart, brain, endocrine glands, gastrointestinal tract, skin, skeleton, and peripheral nerves. Phenotypes of DM1 may be classified as congenital, juvenile, classical, or late onset. DM2 is a disorder of the middle or older age and usually has a milder course compared to DM1. DM1 is due to a CTG-repeat expansion > 50 repeats in the non-coding 3' UTR of the DMPK-gene. DM2 is caused by a CCTG-repeat expansion to 75 - 11 000 repeats in intron-1 of the CNBP/ZNF9 gene. Mutant pre-mRNAs of both genes aggregate within the nucleus (nuclear foci), which sequester RNA-binding proteins and result in an abnormal protein expression via alternative splicing in downstream effector genes (toxic RNA diseases). Other mechanisms seem to play an additional pathogenetic role. Clinical severity of DM1 increases from generation to generation (anticipation). The higher the repeat expansion the more severe the DM1 phenotype. In DM2 severity of symptoms and age at onset do not correlate with the expansion size. Contrary to DM2, there is a congenital form and anticipation in DM1.

Dystrophia myotonica type 1 presenting with dysarthria: A case report and literature review

“…It typically affects skeletal and smooth muscle, as well as the endocrine and central nervous systems (5,6,13). The disorder is characterized by progressive myopathy, myotonia and the involvement of multiple organs.…”

“…DM affects the skeletal muscles, ocular lens, lungs, heart and gastrointestinal tract, as well as the endocrine and central nervous systems (1,2,4). The clinical manifestations of DM vary, however typical symptoms include myotonia, weakness and atrophy of the skeletal muscles (5,6). Poor sleep quality, fatigue and excessive daytime sleepiness have an important effect on the quality of life of DM patients.…”

“…Based on the mutations that occur within the DM protein kinase ( DMPK ) gene, DM is categorized as two distinct types: Types 1 and 2 (5). DM type 1 is caused by expansion of CTG triplet repeat in the 3′ untranslated region of the DMPK gene on chromosome 19q13.3 (5). DM type 2 is caused by the progressive expansion of a CCTG tetramer repeat in ZNF9 .…”

Comment on “Symptomatic Trifascicular Block in Steinert’s Disease: Is It Too Soon for a Pacemaker?”

“…Since MD1 is characterised by the phenomenon of anticipation [5], the CTG-repeat size may have expanded in subsequent generations and patients in preceding generations may be only mildly affected. Were all available family members investigated for such mild manifestations of the disease?…”

“…Did the patient manifest with other typical clinical manifestation of MD1 such as frontal baldness, cataract, myopathic face, distal weakness, wasting, or myotonia [5]?…”