Myotonic Dystrophies Type 1 and 2: A Summary on Current Aspects
Section snippets
Molecular Genetics of DM Type 1
In 1992, DM type 1 (DM1) on chromosome 19 was shown to be caused by an expanded CTG repeat in the 3′ untranslated region of the dystrophia myotonica-protein kinase (DMPK) gene.3, 4, 12, 13, 14, 15 The incidence of DM1 is 13:100,000; the prevalence is 2 to 5/100,000 in the congenital form 1: 3500.3, 4 The CTG expansions in DM1 differ from 80 to more than 4,000 repeats in affected patients, with clinically unaffected patients having repeats of 50 to 100 CTGs. Somatic instability has been reported
DM1
Manifestation varies from the pre-/postnatal period to adulthood: within the broad spectrum of clinical symptoms, there are some distinct phenotypes according to the age of onset and the number of CTG repeats. Genotype phenotype correlations revealed a slight increase of CTG repeats in the juvenile-adult form, a stronger increase in patients with childhood onset, and the largest CTG repeats (>1,500) in congenital myotonic dystrophy.3, 4, 25 Clinicians should be able to recognize these different
Monitoring and Therapy of All Types of DM
Monitoring should include conduction studies, ultrasound of the heart, and respiratory function analysis. Although there is no causative therapy available so far, symptomatic therapy should include the following.39, 40, 41, 42
In congenital DM1, symptomatic therapy should include (1) stabilization of respiratory and feeding difficulties, (2) orthopedic surgery if necessary, (3) physiotherapy, (4) pulmonary and cardiac investigations, (5) treatment of motor and mental handicaps, and (6)
Outlook
Although myotonic dystrophy was noticed around 100 years ago, we still become aware of new aspects and types of this puzzling multisystemic disorder. By further uncovering the RNA pathomechanism and creating new RNA therapy strategies, specific tools may be found for treatment of these disorders.
References (42)
- et al.
Proximal myotonic dystrophy—A family with autosomal dominant muscular dystrophy, cataracts, hearing loss and hypogonadism: Heterogeneity of proximal myotonic syndromes?
Neuromuscul Disord
(1997) - et al.
Clinical and genetic characteristics of a five-generation family with a novel form of myotonic dystrophy (DM2)
Neuromuscul Disord
(1999) - et al.
RNA pathogenesis of the myotonic dystrophies
Neuromuscul Disord
(2005) - et al.
Confirmation of DM2 (CCTG)n expansion mutation in PROMM/PDM patients of different European origins: A single shared haplotype indicates ancestral founder effects
Am J Hum Genet
(2003) - et al.
Myotonic dystrophy type 2: Human founder haplotype and evolutionary conservation of the repeat tract
Am J Hum Genet
(2003) - et al.
Persistent pulmonary hypertension in newborn infants with congenital myotonic dystrophy
J Pediatr
(1994) - et al.
123rd ENMC international workshop: Management and Therapy in Myotonic Dystrophy, 6-8 February 2004, Naarden, The Netherlands
Neuromuscul Disord
(2005) - et al.
140th ENMC International Workshop: Myotonic Dystrophy DM2/PROMM and other myotonic dystrophies with guidelines on management
Neuromuscul Disord
(2006) Myopathologische Beiträge 1. Über das klinische und anatomische Bild des Muskelschwunds der Myotoniker
Dtsch Zeitschr Nervenheilk
(1909)- et al.
Myotonia atrophica
Brain
(1909)
Major problems in neurology, in Myotonic Dystrophy
Myotonic dystrophy
Über familiäre atrophische Myotonie
Dtsch Zeitschr Nervenheilk
Myotonische Dystrophie (atrophische myotonie)
Über myotonische Dystrophie mit Katarakt
Graefes Arch Klin Ophthalmol
Proximal myotonic myopathy: A new dominant disorder with myotonia, muscle weakness, and cataracts
Neurology
Myotonic dystrophy with no trinucleotide repeat expansion
Ann Neurol
Cloning of the essential myotonic dystrophy region and mapping of the putative defect
Nature
Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy
Nature
Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy
Nature
Myotonic dystrophy mutation: An unstable CTG repeat in the 3′ untranslated region of the gene
Science
Cited by (105)
Orthopedic Surgery in Neuromuscular Disorders
2021, Neuromuscular Disorders: Treatment and ManagementHypotonic syndrome manifestation of neuromuscular hereditary disease in infants
2018, Revista Medica Clinica Las CondesMyopathies
2018, Essentials of Physical Medicine and Rehabilitation: Musculoskeletal Disorders, Pain, and Rehabilitation
Supported in part by the German Network on Muscular Dystrophies (MD-NET, 01GM0302) funded by the German Ministry of Education and Research (BMBF, Bonn, Germany).