1. Background

• Myotonic Dystrophy (MD) belongs to a growing family of disorders where the genetic mutation involves unstable trinucleotide repeats (C_G):

• in this family of disorders, the number of repeats tends to increase with succeeding generations ("genetic anticipation")
• in Myotonic Dystrophy:
  • Dr. R. Korneluk at CHEO was the first to isolate the MD gene and an unstable part of the gene was identified characterized by numerous repeats of single trinucleotide sequences containing the bases cytosine, thymine, and guanine (CTG)
  • in normal individuals, there are between 5-35 CTG repeats but in those with CMD, there may be between 80-2000 CTG repeats
  • the MD gene may code for a kinase - kinases regulate their own activity and the activity of other cellular proteins by transferring phosphate groups

2. Genetic Defect

• genetic defect -> amplification of the sequence of unstable trinucleotide repeats (CTG) in the 3' region of the gene to greater than 80 -> disturbance in muscle fibre maturation with incomplete differentiation
• the number of CTG repeats may affect the phenotype and the risk for amplification to the full mutation allele:

1. Neurological Manifestations

• severe generalized hypotonia and diffuse muscle weakness
• infantile hypotonia
• bilateral facial weakness
• unilateral or bilateral ptosis
• tented upper lip
• swallowing and feeding problems - gavage feeds
• neck weakness
• respiratory distress
• abdominal distention due to poor peristalsis
• undescended testes
• no myotonia or ophthalmoplegia

• if infant survives:
  • gradual improvement in muscle strength and tone, sucking and swallowing
  • persistence of facial weakness
  • mental retardation (in 80% of cases)
  • appearance of classic features of myotonic dystrophy later in childhood with:
    • arrhythmias
    • cataracts
    • frontal baldness
    • insulin dependent diabetes mellitus (IDDM)
    • loss of body hair
    • testicular atrophy

2. Musculoskeletal Manifestations

• arthrogryposis of multiple joints +/- cervical spine
• congenital dislocation of hips
• foot deformities - talipes equinovarus

1. Diagnostic

• identification of amplified CTG sequences in the MD gene of affected individuals

2. Serum

• normal CPK

3. EMG

• abnormal by age 3 years

4. Muscle Biopsy

• infant - small undifferentiated muscle fibres
  • peripheral halos devoid of oxidative capacity, mitochondria, and organized myofibrils
• child - type 1 fibre type atrophy
  • central nuclei, sarcoplasmic masses, ring fibres

1. Supportive

• no treatment for the disease
• multidisciplinary approach
  • Paediatrics - support respiratory and gastrointestinal problems, promote ambulation and physiotherapy, moniter for deformities
  • Neurology - manage myotonic dystrophy
  • Surgery - moniter and correct deformities
  • Genetics - genetic counselling, prenatal diagnosis