myotonic dystrophy; Steinert disease; myotonia dystrophica
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Etiology
- trinucleotide repeat (CTG) expansion in 3' untranslated region of genes for:
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
- autosomal dominant
- aberrant gene: myotonin protein kinase gene, chromosome 19 (myotonic dystrophy type 1)
- disease expression is variable
- disease tends to worsen in subsequent generations due to a tendency for the trinucleotide expansion to increase in size
- many affected parents are asymptomatic
- MBNL2 & MBNL3 colocalize with nuclear foci of retained expanded-repeat transcripts
- DMWD may play role in development of mental symptoms
- other implicated genes PEPD, HNRNPH1
Clinical manifestations
- age at onset: 15-30 years
- myotonia (impaired muscle relaxation)
- muscle weakness
- wasting of temporalis muscle
- slow rate of progression
- alopecia, male-pattern baldness
- ptosis
- nasal speech
- cataracts[4]
- cardiac conduction abnormalities occur frequently
- most patients without symptoms
- may progress to complete heart block & sudden death
- cardiomyopathy[4]
- diabetes mellitus[4]
- cognitive impairment
Laboratory
- serum creatine kinase is normal
- PCR/southern blot
Diagnostic procedures
Complications
- nocturnal ventilatory impairment may precede awakend-state hypoventilation
- non-ischemic cardiomyopathy progressing to cardiogenic shock[5]
Management
- symptomatic
- ankle-foot orthoses are useful for patients with foot drop
- phenytoin may be useful
- consider cardiac pacemakers for patients with symptomatic conduction system abnormalties
- nocturnal non-invasive positive pressure ventilation (NPPV) if evidence of hypoventilation[4]
More general terms
More specific terms
Additional terms
References
- ↑ Ross CA et al Genes with triplet repeats: candidate mediators of neuropsychiatric disorders. TINS 16:254 1993 PMID: https://www.ncbi.nlm.nih.gov/pubmed/7689767
- ↑ Klesert TR et al Trinucleotide repeat expansion at the myotonic dystrophy locus reduces expression of DMAHP. Nature Genetics 16:402-6 1997 PMID: https://www.ncbi.nlm.nih.gov/pubmed/9241282
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/9241283
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 17. American College of Physicians, Philadelphia 1998, 2006, 2009, 2015
- ↑ 5.0 5.1 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: https://www.ncbi.nlm.nih.gov/pubmed/26398074
- ↑ Udd B, Krahe R. The myotonic dystrophies: molecular, clinical, and therapeutic challenges. Lancet Neurol. 2012 Oct;11(10):891-905 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22995693
- ↑ Turner C, Hilton-Jones D. Myotonic dystrophy: diagnosis, management and new therapies. Curr Opin Neurol. 2014 Oct;27(5):599-606. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25121518 Review.
- ↑ Thornton CA. Myotonic dystrophy. Neurol Clin. 2014 Aug;32(3):705-19, viii. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25037086 PMCID: PMC4105852 Free PMC article. Review.