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myotonic dystrophy; Steinert disease; myotonia dystrophica

Etiology: - trinucleotide repeat (CTG) expansion in 3' untranslated region of genes for: a) myotonin protein kinase b) cellular nucleic acid-binding protein Epidemiology: - 1 in 8000 live births - most common form of adult onset muscular dystrophy - most common myotonic disorder [4] Pathology: - myotonia - reduction in expression of DMAHP homeobox gene, in myoblasts, muscle & myocardium - the greater the trinucleotide expansion, the less the amount DMAHP expression Genetics: 1) autosomal dominant 2) aberrant gene: myotonin protein kinase gene, chromosome 19 (myotonic dystrophy type 1) 3) disease expression is variable 4) disease tends to worsen in subsequent generations due to a tendency for the trinucleotide expansion to increase in size 5) many affected parents are asymptomatic 6) MBNL2 & MBNL3 colocalize with nuclear foci of retained expanded-repeat transcripts 7) DMWD may play role in development of mental symptoms 8) other implicated genes PEPD, HNRNPH1 Clinical manifestations: 1) age at onset: 15-30 years 2) myotonia (impaired muscle relaxation) a) especially grip myotonia b) often worse in cold weather 3) muscle weakness a) facial involvement early b) initial weakness: distal extremities - myopathic waddling gait [4] c) weakness of the forearm & peroneal muscles [4] 4) wasting of temporalis muscle 5) slow rate of progression 6) alopecia, male-pattern baldness 7) ptosis 8) nasal speech 9) cataracts [4] 9) cardiac conduction abnormalities occur frequently a) most patients without symptoms b) may progress to complete heart block & sudden death 10) cardiomyopathy [4] 11) diabetes mellitus [4] 12) cognitive impairment Laboratory: 1) serum creatine kinase is normal 2) PCR/southern blot Special laboratory: - electrocardiogram: heart block Complications: - nocturnal ventilatory impairment may precede awakend-state hypoventilation - non-ischemic cardiomyopathy progressing to cardiogenic shock [5] Management: 1) symptomatic 2) ankle-foot orthoses are useful for patients with foot drop 3) phenytoin may be useful 4) consider cardiac pacemakers for patients with symptomatic conduction system abnormalties 5) nocturnal non-invasive positive pressure ventilation (NPPV) if evidence of hypoventilation [4]

Related

muscular dystrophy

Specific

myotonic dystrophy 1 myotonic dystrophy 2 (proximal myotonic myopathy)

General

myotonic disorder trinucleotide repeat expansion disease

Database Correlations

OMIM correlations

References

  1. Ross CA et al Genes with triplet repeats: candidate mediators of neuropsychiatric disorders. TINS 16:254 1993 PMID: 7689767
  2. Klesert TR et al Trinucleotide repeat expansion at the myotonic dystrophy locus reduces expression of DMAHP. Nature Genetics 16:402-6 1997 PMID: 9241282
  3. Thornton CA et al Expansion of the myotonic dystrophy CTG repeat reduces expression of the flanking DMAHP gene. Nature Genetics 16:407-9 1997 PMID: 9241283
  4. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 17. American College of Physicians, Philadelphia 1998, 2006, 2009, 2015
  5. Wheeler TM, Baker JN, Chad DA et al Case Records of the Massachusetts General Hospital. Case 30-2015: A 50-Year-Old Man with Cardiogenic Shock. N Engl J Med. 2015 Sep 24;373(13):1251-61 PMID: 26398074
  6. Udd B, Krahe R. The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol. 2012 Oct;11(10):891-905 PMID: 22995693
  7. Turner C, Hilton-Jones D. Myotonic dystrophy: diagnosis, management and new therapies. Curr Opin Neurol. 2014 Oct;27(5):599-606. PMID: 25121518 Review.
  8. Thornton CA. Myotonic dystrophy. Neurol Clin. 2014 Aug;32(3):705-19, viii. PMID: 25037086 PMCID: PMC4105852 Free PMC article. Review.