Type 1 Myotonic Dystrophy
- Pathophysiology
- CTG trinuclear repeat expansion on DMPK gene (Chr 19q13) → production of altered mRNA → traps proteins to form clumps in cells → cell death
- Clinical presentation
- Present as youth
- Distal extremity weakness that may progress proximally.
- Specific neck flexor involvement may be apparent early
- Typical facial features include
- Temporalis atrophy
- A tent-shape mouth caused by facial muscle atrophy.
- Delayed relaxation (action myotonia) of hand-grip or eyelid closure
- Percussing bellies of affected muscles (eg, abductor pollicis brevis) results in prolonged muscle contraction with delayed relaxation (percussion myotonia).
- Systemic involvement
- Cardiac conduction defects may lead to sudden cardiac death
- Need Pacemaker
- Cataracts
- Gastrointestinal motility issues
- Sleep apnea
- Testicular atrophy
- High rates of foetal loss to mothers with DM1 are common.
- Mild intellectual disability
- Those with congenital DM1 born to mothers with DM1 may have severe intellectual disability.
- Diagnostic test results
- Normal to mildly elevated creatine kinase (CK) levels
- Normal sensory and motor nerve conduction studies,
- Myotonic discharges on needle EMG of several muscles.
- Diagnosis is with genetic testing results that show a CTG trinucleotide repeat expansion (> 50 repeats) of DMPK on chromosome 19q13.2.
- The size of the unstable CTG repeat expansion is directly related to the severity of clinical weakness.
- Genetic anticipation is seen, with children of affected parents having a higher number of repeats and more severe clinical phenotype.
Type 2 Myotonic Dystrophy
- Type 2 (DM2) also affects many organ systems causing weakness, cardiac conduction defects, cataracts, hypogammaglobulinemia, and testicular atrophy.
- Pathophysiology
- CTG trinuclear repeat expansion on ZNF 9 gene (Chr 3) → production of altered mRNA → traps proteins to form clumps in cells → cell death
- Clinical features
- Onset is typically in early to middle adulthood.
- Intermittent stiffness and proximal leg muscle pain that may be described as debilitating or burning.
- Proximal and distal weakness progresses slowly and clinical myotonia may not be as prevalent as in DM1.
- Symptoms and severity of clinical weakness are heterogeneous, even within a family.
- Intellectual disability is less common in adults with DM2 compared with DM1
- Diagnostic test
- Mildly elevated CK,
- Normal motor and sensory nerve conduction studies,
- Needle EMG myotonic discharges even in patients without clinical myotonia.
- Muscle biopsy shows nonspecific myopathic features (eg, increased internal nuclei, fiber size variability with type 2 fiber atrophy, small angulated fibers, and atrophic fibers with pyknotic nuclear clumps).
- Genetic test results show CCTG repeat expansion NF9 intron 1 on chromosome 3.
Key clinical and genetic differences of DM1 and DM2
ㅤ | Type 1 (DM1) | Type 2 (DM2) |
Inheritance | Autosomal dominant | Autosomal dominant |
Genetic mutation | CTG trinucleotide repeat expansion on DMPK gene on chromosome 19q13 | CCTG tetranucleotide expansion on ZNF9 gene on chromosome 3 |
Main clinical findings | Facial and distal weakness | Proximal weakness |
Myotonia | Grip myotonia, no fluctuation | Variable mild grip myotonia |
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