Type 1 myotonic dystrophy

Classification according to ICD-10
G71.1	Myotonic Syndrome Dystrophia myotonica (Curschmann-Batten-Steinert Syndrome)
ICD-10 online (WHO version 2019)

The myotonic dystrophy type 1 , short- DM1 , also myotonia dystrophic , myotonic dystrophy , Crohn Curschmann Steinert or Crohn Curschmann Steinert Batten , named after the Erstbeschreibern Hans Curschmann (German internist, 1875-1950) and Hans Gustav Wilhelm Steinert (German Internist , 1875–1911) is a form of myotonic muscle disease with muscular dystrophy , lens opacity and hormonal disorder ( hypogonadism ). With an incidence of 5 / 100,000 per year, it is the most common myotonia and affects boys more often than girls. The inheritance of the progressive multisystem diseases is autosomal dominant .

to form

A distinction is made between an inborn ( congenital ) form with a manifestation at birth as a " floppy infant " (muscular newborn) from an adult form with a disease peak in the second to third decade of life . The congenital form is usually inherited from the mother. There is an anticipation , which means an increase in symptoms and expression, as well as a decrease in the age of onset with inheritance from parents to offspring.

Clinically, the adult form manifests itself through progressive muscle weakness, especially in the face and neck area and in the legs, cardiac arrhythmias , lens opacity , hormonal disorders ( hypogonadism ) with testicular atrophy , baldness or menstrual disorders , pregnancy complications and, with progressive disease, severe pain in the joints and muscle convulsions.

root cause

The cause of myotonic dystrophy type 1 is an autosomal dominant inherited genetic defect on chromosome 19 with (CTG) _n trinucleotide repeat expansion (unstable CTG repeats in the DMPK gene ). The consequence of this defect is the reduced production of myotonin protein kinase and the damage it causes to the muscle fiber membrane and the SERCA calcium pump . The disease is one of the adult segmental progeroid syndromes.

Diagnosis

The examination and diagnosis is carried out with measurement of the electrical muscle activity in the electromyogram (EMG) (formerly described as the dive bomber noise ) as well as direct genetic diagnosis from leukocytes . However, the informative value of the expression is limited, as the trinucleotide extension varies greatly in different types of tissue. This also applies in particular to prenatal diagnosis from chorionic villi .

Clinic, family history and laboratory tests are also used (increased creatine kinase (CK) and insulin , decreased sex hormones). In terms of differential diagnosis, progressive muscular dystrophy and myotonia congenita Thomsen should be considered.

Prognosis, therapy

The disease cannot be cured. Life expectancy is reduced to an average of 50–60 years (death from heart failure).

Treatment consists of physiotherapy and drug therapy with mexiletine , tocainide or phenytoin . Sex hormones and pacemakers may also be necessary. Fenoterol for the inhibition of labor during pregnancy or for the treatment of obstructive airways diseases, like succinylcholine, are contraindicated in anesthesia, since both substances can massively increase myotonic symptoms. Propofol anesthesia is preferred.

literature

Hans Curschmann: About familial atrophic myotonia . In: German Journal of Neurology (now: Journal of Neurology) . tape 45 , no. 3 . Steinkopf, 1912, ISSN 0340-5354 , p. 161-202 , doi : 10.1007 / BF01629597 .
TD Bird: Myotonic dystrophy type 1. In: MP Adam, HH Ardinger, RA Pagon et al. (Ed.): GeneReviews. University of Washington, Seattle 1993–2019, September 17, 1999, updated December 6, 2018.
Davor Lessel, Christian Kubisch: Genetically determined syndromes with signs of premature aging. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f., July 22, 2019, pp. 489–496, here: pp. 491–494.

Individual evidence

↑ S. Hino, S. Kondo, H. Sekiya et al .: Molecular mechanisms responsible for aberrant splicing of SERCA1 in myotonic dystrophy type 1 . In: Hum. Mol. Genet. tape 16 , no. December 23 , 2007, pp. 2834-2843 , doi : 10.1093 / hmg / ddm239 , PMID 17728322 .

↑ Davor Lessel, Christian Kubisch: Genetically determined syndromes with signs of premature aging. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f., July 22, 2019, pp. 489–496, here: pp. 491–494.

[1] S. Hino, S. Kondo, H. Sekiya et al .: Molecular mechanisms responsible for aberrant splicing of SERCA1 in myotonic dystrophy type 1 . In: Hum. Mol. Genet. tape 16 , no. December 23 , 2007, pp. 2834-2843 , doi : 10.1093 / hmg / ddm239 , PMID 17728322 .

[2] Davor Lessel, Christian Kubisch: Genetically determined syndromes with signs of premature aging. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f., July 22, 2019, pp. 489–496, here: pp. 491–494.