Myotonic dystrophy (DM) is the most common form of myotonic myopathy, with an estimated prevalence of 1 in 7,000 people, though milder cases often go undiagnosed.

Overview

This multisystem disorder is inherited as an autosomal dominant trait and can affect various systems, including:

• Skeletal and smooth muscle
• Eyes
• Heart
• Endocrine system
• Central nervous system

The clinical spectrum ranges from mild to very severe, categorized into three overlapping phenotypes:

1. Mild
2. Classic
3. Congenital

Genetic Basis of Myotonic Dystrophy

1. Myotonic Dystrophy Type 1 (DM1)

   • Cause: CTG trinucleotide expansion in the untranslated region of the DMPK gene (dystrophia myotonica–protein kinase) located on chromosome 19q13.3.
   • Genetic Anticipation: The length of the CTG repeat often increases significantly between generations, leading to more severe manifestations in offspring.

2. Myotonic Dystrophy Type 2 (DM2)

   • Previously known as proximal myotonic myopathy, DM2 is much rarer and typically not observed in childhood.

Classic Myotonic Dystrophy

Classic myotonic dystrophy (type 1, DM1) exhibits wide variability in clinical severity. The typical age of onset is in the twenties or thirties, though subtle signs such as facial weakness and myotonia may appear during childhood. Some individuals may present with minimal symptoms like cataracts, mild myotonia, or diabetes mellitus.

Clinical Features

1. Muscular Atrophy and Weakness

   • Characteristic Distribution:
     • Facial muscles: Atrophy of masseters and temporalis muscles results in a long, thin face and hollowed temporal fossae.
     • Neck and shoulder girdle muscles: Involvement of the sternocleidomastoid and shoulder girdle muscles.
     • Limb muscles: Wasting of the brachioradialis, hand intrinsic muscles, and anterior compartment of the leg, leading to foot drop.
   • Progression:
     • Childhood-onset cases may progress to significant weakness in adulthood, occasionally resulting in wheelchair confinement.

2. Myotonia

   • Definition: Slowing of muscle relaxation following voluntary contraction.
   • Clinical Observation: Best seen in the eyelids or hand grip.
   • Elicited Myotonia: Percussion of muscles, such as the thenar eminence, can induce sustained contraction (e.g., thumb opposition for several seconds).

3. Muscle Pain and Respiratory Compromise

   • Muscle Pain: Prominent in many patients.
   • Respiratory Issues: Advanced disease can lead to respiratory muscle weakness, aspiration, and pneumonia.

4. Smooth Muscle Involvement

   • Symptoms include dysphagia, constipation, diarrhea, or incontinence.

5. Systemic Manifestations

   • Ocular:
     • Posterior cataracts: Often develop after the first decade and may be the presenting feature.
   • Cardiac:
     • Conduction defects, arrhythmias, and risk of sudden cardiac death 
   • Endocrine:
     • Hypogonadism, frontal balding, and insulin resistance 

6. Neurocognitive and Behavioral Features

   • Intellectual Impairment: Common in classic DM1.
   • Personality Traits: Avoidant, obsessive-compulsive, and passive-aggressive tendencies 

7. Sleep Disorders

   • Hypersomnia and sleep apnea are well-recognized complications=

Complications and Prognosis

• Reduced Lifespan:
  • Most often due to respiratory failure, pneumonia, or cardiovascular complications such as arrhythmias 
• Cardiac Risk:
  • Conduction defects and arrhythmias are the most critical complications due to their potential for sudden cardiac death.

Mild Myotonic Dystrophy

Children with mild myotonic dystrophy often present with:

• Static Cognitive Issues:
  • Cognitive impairments may manifest during childhood, typically remaining stable over time.
• Muscle Weakness:
  • Weakness is generally mild and proximally predominant, often not significantly impacting early motor function.
• Myotonia:
  • Myotonia is subtle and frequently unreported by patients due to its mild nature.
  • Requires careful examination to detect, such as through percussion of muscles or observation during hand grip.

Clinical Considerations

• Early recognition of cognitive issues can guide supportive interventions.
• Regular monitoring for muscle weakness progression and early detection of myotonia are important for comprehensive care.
• Given the mild nature of symptoms, some cases may remain undiagnosed unless actively investigated.

Congenital Myotonic Dystrophy

Key Features:

• Nature: Severe early-onset myopathy characterized by prenatal and perinatal manifestations.
• Prenatal Indicators: Decreased fetal movement, polydramnios, talipes equinovarus (clubfoot), and breech presentation.
• Perinatal Presentation:
  • Hypotonia and muscle weakness.
  • Facial diplegia with a distinctive tented upper lip.
  • Respiratory insufficiency in approximately 80% of cases, often requiring ventilatory support.
  • Feeding difficulties, commonly necessitating gavage feeding.

Diagnosis:

• Differential Diagnosis:
  • Can be confused with congenital myopathies or muscular dystrophies.
  • Facial weakness distribution and overall appearance are diagnostic clues.
• Family Examination:
  • Evaluation of the mother for signs of mild weakness and myotonia (hallmarks of adult-onset myotonic dystrophy) is often diagnostic.

Prognosis and Progression:

• Early Mortality:
  • High mortality in infancy due to respiratory muscle involvement.
• Improvements in Survivors:
  • Gradual motor improvements; survivors usually achieve ambulation.
  • Progressive myopathy develops later, mirroring the classic form of myotonic dystrophy.
  • Risk of cardiac complications (arrhythmias, cardiomyopathy) beginning in the first decade.
• Neurological Aspects:
  • Severe static cognitive deficits are common.
  • Myotonia (muscle stiffness) is typically absent until later childhood (≥3–4 years), sometimes detected only in adolescence.

Diagnosis

1. Laboratory and Diagnostic Studies:

   • Serum Creatine Kinase (CK): Mild to moderate elevation.
   • Electromyography (EMG): Identifies myotonic discharges, primarily in distal muscles of older children.
   • Muscle Biopsy:
     • Not routinely required.
     • Shows increased internal nuclei, atrophic fibers, and minimal dystrophic changes (can mimic centronuclear myopathy).

2. Genetic Testing:

   • Causative Mutation: Expansion of the CTG trinucleotide repeat in the DMPK gene on chromosome 19q13.3.
   • Normal Range: 5–34 repeats.
   • Pathological Repeat Sizes:
     • Premutation: 35–49 repeats (risk for larger expansions in offspring).
     • Classic DM1: 100–1000 repeats.
     • Congenital DM1: >2000 repeats, almost exclusively maternally inherited.
   • Anticipation:
     • Increasing repeat size in successive generations.
     • Strong maternal transmission bias.
   • Molecular Testing: Confirms diagnosis with near 100% accuracy; enables prenatal and postnatal diagnosis.

3. Pathophysiology:

   • Expanded CTG repeat leads to aberrant RNA processing, affecting alternative splicing of various genes (e.g., chloride channel leading to myotonia, insulin receptor leading to diabetes).

Management and Surveillance

1. Multidisciplinary Monitoring:

   • Cardiac:
     • Annual ECG or Holter monitoring for conduction defects.
   • Pulmonary:
     • Regular pulmonary function tests to assess respiratory insufficiency.
   • Swallowing:
     • Periodic evaluation to prevent aspiration and optimize feeding strategies.

2. Nutritional Support:

   • Many patients require gavage feeding due to swallowing difficulties.

3. Symptom-Specific Management:

   • Myotonia:
     • Rarely severe enough to require treatment.
   • Myalgia:
     • Symptomatic treatment as needed.
   • Excessive Daytime Sleepiness:
     • Modafinil is effective in adults but not formally studied in children.

4. Prognosis:

   • Life expectancy is reduced, with significant early mortality in congenital cases.
   • Causes of Death:
     • Pneumonia.
     • Sudden cardiac death.
     • Progressive respiratory failure.
   • Survival:
     • 25% mortality by age 5 in congenital cases.
     • 50% survive into their mid-30s.
   • Functional Outcomes:
     • Cognitive impairment prevents most from achieving independent living.