Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Myotonic Dystrophy Type 1 (Curschmann-Steinert Disease) [G71.1]

OMIM numbers: 160900, 605377 (DMPK)

Dr. rer. biol. hum. Soheyla Chahrokh-Zadeh, Dr. med. Imma Rost

Scientific Background

Myotonic dystrophies, multisystemic diseases with autosomal dominant inheritance pattern, represent the most frequently occurring muscular dystrophies in adults. The incidence of myotonic dystrophy type 1 (DM1) is estimated to be 1 in 8,000. First signs and symptoms such as myotonia, i.e. delayed relaxation of a contracted muscle, commonly first occur during early adult age. Additional signs and symptoms are muscle weakness and fatigability as well as swallowing difficulty, a long face with little facial expression, cataract, diabetes mellitus, cardiac arrhythmia, early development of frontal baldness and testicular atrophy in men. The clinical picture of DM1 is categorized into four, partially overlapping phenotypes: asymptomatic, mild, classic and neonatal type. The connatal form is mainly characterized by severe muscular hypotonia frequently with clubfoot and usually accompanied by respiratory insufficiency and poor sucking. Psychomotor development is frequently delayed. The form only occurs in DM1 and is predominantly seen if the disease was passed on by the mother.

DM1 is caused by a CTG repeat expansion in the 3’ untranslated region of the DMPK gene on chromosome 19, which encodes a protein kinase. DM2 (proximal myotonic myopathy=PROMM OMIM-Nr: 602688), which is important regarding differential diagnosis, is caused by expansion of a CCTG repeat in intron 1 of the ZNF9 gene on chromosome 3. The phenomenon of anticipation – i.e. lower age of onset and/or more severe signs and symptoms as the disease is passed on from one generation to the next – is particularly strong in DM1. Healthy individuals have 5-36 repeats in the DMPK gene, DM patients have up to approx. 1,000; children with the congenital form have over 1,000 repeats.

In predictive genetic testing, at-risk, asymptomatic individuals are tested, usually first-degree relatives of affected patients. According to the Genetic Diagnosis Act (GenDG) genetic counseling should be offered along with any genetic diagnostic procedure. In the case of predictive genetic testing, genetic counseling must be carried out prior to testing as well as after having received the result, unless there exists a written waiver of the at-risk person after having received written information on the content of the counseling.